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Search </button> </form> <nav class="minerva-user-navigation" aria-label="User navigation"> </nav> </div> </header> <main id="content" class="mw-body"> <div class="banner-container"> <div id="siteNotice"></div> </div> <div class="pre-content heading-holder"> <div class="page-heading"> <h1 id="firstHeading" class="firstHeading mw-first-heading">Gene silencing</h1> <div class="tagline"></div> </div> <ul id="p-associated-pages" class="minerva__tab-container"> <li class="minerva__tab selected mw-list-item"> <a class="minerva__tab-text" href="/wiki/Gene_silencing" rel="" data-event-name="tabs.main">Article</a> </li> <li class="minerva__tab mw-list-item"> <a class="minerva__tab-text" href="/wiki/Talk:Gene_silencing" rel="discussion" data-event-name="tabs.talk">Talk</a> </li> </ul> <nav class="page-actions-menu"> <ul id="p-views" class="page-actions-menu__list"> <li id="language-selector" class="page-actions-menu__list-item"> <a role="button" href="#p-lang" data-mw="interface" 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menu__item--page-actions-edit"> Edit </a> </li> </ul> </nav>  <div id="mw-content-subtitle"></div> </div> <div id="bodyContent" class="content"> <div id="mw-content-text" class="mw-body-content"><script>function mfTempOpenSection(id){var block=document.getElementById("mf-section-"+id);block.className+=" open-block";block.previousSibling.className+=" open-block";}</script><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><section class="mf-section-0" id="mf-section-0"> Gene silencing is the <a href="/wiki/Regulation_of_gene_expression" title="Regulation of gene expression">regulation of gene expression</a> in a cell to prevent the expression of a certain <a href="/wiki/Gene" title="Gene">gene</a>.<a href="#cite_note-redberry-1">[1]</a><a href="#cite_note-NCBI-2">[2]</a> Gene silencing can occur during either <a href="/wiki/Transcription_(genetics)" class="mw-redirect" title="Transcription (genetics)">transcription</a> or <a href="/wiki/Translation_(biology)" title="Translation (biology)">translation</a> and is often used in research.<a href="#cite_note-redberry-1">[1]</a><a href="#cite_note-NCBI-2">[2]</a> In particular, methods used to silence genes are being increasingly used to produce <a href="/wiki/Therapeutics" class="mw-redirect" title="Therapeutics">therapeutics</a> to combat cancer and other diseases, such as <a href="/wiki/Infectious_diseases" class="mw-redirect" title="Infectious diseases">infectious diseases</a> and <a href="/wiki/Neurodegenerative_disorders" class="mw-redirect" title="Neurodegenerative disorders">neurodegenerative disorders</a>. Gene silencing is often considered the same as <a href="/wiki/Gene_knockdown" title="Gene knockdown">gene knockdown</a>.<a href="#cite_note-Hood-3">[3]</a><a href="#cite_note-Mocellin-4">[4]</a> When genes are silenced, their expression is reduced.<a href="#cite_note-Hood-3">[3]</a><a href="#cite_note-Mocellin-4">[4]</a> In contrast, when genes are knocked out, they are completely erased from the organism's <a href="/wiki/Genome" title="Genome">genome</a> and, thus, have no expression.<a href="#cite_note-Hood-3">[3]</a><a href="#cite_note-Mocellin-4">[4]</a> Gene silencing is considered a gene knockdown mechanism since the methods used to silence genes, such as <a href="/wiki/RNAi" class="mw-redirect" title="RNAi">RNAi</a>, <a href="/wiki/CRISPR" title="CRISPR">CRISPR</a>, or <a href="/wiki/SiRNA" class="mw-redirect" title="SiRNA">siRNA</a>, generally reduce the expression of a gene by at least 70% but do not eliminate it[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>]. Methods using gene silencing are often considered better than gene knockouts[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] since they allow researchers to study essential genes that are required for the <a href="/wiki/Animal_models" class="mw-redirect" title="Animal models">animal models</a> to survive and cannot be removed. In addition, they provide a more complete view on the development of diseases since diseases are generally associated with genes that have a reduced expression.<a href="#cite_note-Hood-3">[3]</a> <style data-mw-deduplicate="TemplateStyles:r886046785">.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 ul{display:none}</style><div class="toclimit-3"><div id="toc" class="toc" role="navigation" aria-labelledby="mw-toc-heading"><input type="checkbox" role="button" id="toctogglecheckbox" class="toctogglecheckbox" style="display:none"><div class="toctitle" lang="en" dir="ltr"><h2 id="mw-toc-heading">Contents</h2><label class="toctogglelabel" for="toctogglecheckbox"></label></div> <ul> <li class="toclevel-1 tocsection-1"><a href="#Types">1 Types</a> <ul> <li class="toclevel-2 tocsection-2"><a href="#Transcriptional">1.1 Transcriptional</a></li> <li class="toclevel-2 tocsection-3"><a href="#Post-transcriptional">1.2 Post-transcriptional</a></li> <li class="toclevel-2 tocsection-4"><a href="#Meiotic">1.3 Meiotic</a></li> </ul> </li> <li class="toclevel-1 tocsection-5"><a href="#Research_methods">2 Research methods</a> <ul> <li class="toclevel-2 tocsection-6"><a href="#Antisense_oligonucleotides">2.1 Antisense oligonucleotides</a></li> <li class="toclevel-2 tocsection-7"><a href="#Ribozymes">2.2 Ribozymes</a></li> <li class="toclevel-2 tocsection-8"><a href="#RNA_interference">2.3 RNA interference</a></li> <li class="toclevel-2 tocsection-9"><a href="#Three_prime_untranslated_regions_and_microRNAs">2.4 Three prime untranslated regions and microRNAs</a></li> </ul> </li> <li class="toclevel-1 tocsection-10"><a href="#Applications">3 Applications</a> <ul> <li class="toclevel-2 tocsection-11"><a href="#Medical_research">3.1 Medical research</a> <ul> <li class="toclevel-3 tocsection-12"><a href="#Cancer">3.1.1 Cancer</a></li> <li class="toclevel-3 tocsection-13"><a href="#Infectious_disease">3.1.2 Infectious disease</a> <ul> <li class="toclevel-4 tocsection-14"><a href="#Viruses">3.1.2.1 Viruses</a></li> <li class="toclevel-4 tocsection-15"><a href="#Bacteria">3.1.2.2 Bacteria</a></li> </ul> </li> <li class="toclevel-3 tocsection-16"><a href="#Respiratory_diseases">3.1.3 Respiratory diseases</a></li> <li class="toclevel-3 tocsection-17"><a href="#Neurodegenerative_disorders">3.1.4 Neurodegenerative disorders</a> <ul> <li class="toclevel-4 tocsection-18"><a href="#Huntington's_disease">3.1.4.1 Huntington's disease</a></li> <li class="toclevel-4 tocsection-19"><a href="#Amyotrophic_lateral_sclerosis">3.1.4.2 Amyotrophic lateral sclerosis</a></li> </ul> </li> <li class="toclevel-3 tocsection-20"><a href="#Therapeutics_challenges">3.1.5 Therapeutics challenges</a></li> </ul> </li> <li class="toclevel-2 tocsection-21"><a href="#Food">3.2 Food</a></li> </ul> </li> <li class="toclevel-1 tocsection-22"><a href="#See_also">4 See also</a></li> <li class="toclevel-1 tocsection-23"><a href="#References">5 References</a></li> <li class="toclevel-1 tocsection-24"><a href="#External_links">6 External links</a></li> </ul> </div> </div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(1)"><h2 id="Types">Types</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=1" title="Edit section: Types" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-1 collapsible-block" id="mf-section-1"> <div class="mw-heading mw-heading3"><h3 id="Transcriptional">Transcriptional</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=2" title="Edit section: Transcriptional" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <ul><li><a href="/wiki/Genomic_Imprinting" class="mw-redirect" title="Genomic Imprinting">Genomic Imprinting</a></li> <li><a href="/wiki/Paramutation" title="Paramutation">Paramutation</a></li> <li><a href="/wiki/Transposon_silencing" title="Transposon silencing">Transposon silencing</a> (or Histone Modifications)</li> <li>Transgene silencing</li> <li><a href="/wiki/Position_effect" title="Position effect">Position effect</a></li> <li><a href="/wiki/RNA-directed_DNA_methylation" title="RNA-directed DNA methylation">RNA-directed DNA methylation</a></li></ul> <div class="mw-heading mw-heading3"><h3 id="Post-transcriptional">Post-transcriptional</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=3" title="Edit section: Post-transcriptional" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <ul><li><a href="/wiki/RNA_interference" title="RNA interference">RNA interference</a></li> <li><a href="/wiki/RNA_silencing" title="RNA silencing">RNA silencing</a></li> <li><a href="/wiki/Nonsense_mediated_decay" class="mw-redirect" title="Nonsense mediated decay">Nonsense mediated decay</a></li></ul> <div class="mw-heading mw-heading3"><h3 id="Meiotic">Meiotic</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=4" title="Edit section: Meiotic" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <ul><li><a href="/wiki/Transvection_(genetics)" title="Transvection (genetics)">Transvection</a></li> <li>Meiotic silencing of unpaired DNA</li></ul> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(2)"><h2 id="Research_methods">Research methods</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=5" title="Edit section: Research methods" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-2 collapsible-block" id="mf-section-2"> <div class="mw-heading mw-heading3"><h3 id="Antisense_oligonucleotides">Antisense oligonucleotides</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=6" title="Edit section: Antisense oligonucleotides" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <a href="/wiki/Antisense_oligonucleotide" class="mw-redirect" title="Antisense oligonucleotide">Antisense oligonucleotides</a> were discovered in 1978 by <a href="/wiki/Paul_Zamecnik" title="Paul Zamecnik">Paul Zamecnik</a> and Mary Stephenson.<a href="#cite_note-Kole-5">[5]</a> <a href="/wiki/Oligonucleotides" class="mw-redirect" title="Oligonucleotides">Oligonucleotides</a>, which are short <a href="/wiki/Nucleic_acid" title="Nucleic acid">nucleic acid</a> fragments, bind to complementary target mRNA molecules when added to the cell.<a href="#cite_note-Kole-5">[5]</a><a href="#cite_note-Dias-6">[6]</a> These molecules can be composed of single-stranded DNA or RNA and are generally 13–25 nucleotides long.<a href="#cite_note-Dias-6">[6]</a><a href="#cite_note-kurreck-7">[7]</a> The antisense oligonucleotides can affect gene expression in two ways: by using an <a href="/wiki/RNase_H" class="mw-redirect" title="RNase H">RNase H</a>-dependent mechanism or by using a steric blocking mechanism.<a href="#cite_note-Dias-6">[6]</a><a href="#cite_note-kurreck-7">[7]</a> RNase H-dependent oligonucleotides cause the target <a href="/wiki/MRNA" class="mw-redirect" title="MRNA">mRNA</a> molecules to be degraded, while steric-blocker <a href="/wiki/Oligonucleotides" class="mw-redirect" title="Oligonucleotides">oligonucleotides</a> prevent translation of the mRNA molecule.<a href="#cite_note-Dias-6">[6]</a><a href="#cite_note-kurreck-7">[7]</a> The majority of antisense drugs function through the RNase H-dependent mechanism, in which RNase H hydrolyzes the RNA strand of the DNA/RNA <a href="/wiki/Heteroduplex" title="Heteroduplex">heteroduplex</a>.<a href="#cite_note-Dias-6">[6]</a><a href="#cite_note-kurreck-7">[7]</a> expression.<a href="#cite_note-Dias-6">[6]</a> <div class="mw-heading mw-heading3"><h3 id="Ribozymes">Ribozymes</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=7" title="Edit section: Ribozymes" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Ribozyme_mechanism.png" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/Ribozyme_mechanism.png/220px-Ribozyme_mechanism.png" decoding="async" width="220" height="311" class="mw-file-element" data-file-width="745" data-file-height="1053"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 311px;" data-mw-src="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/Ribozyme_mechanism.png/220px-Ribozyme_mechanism.png" data-width="220" data-height="311" data-mw-srcset="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/Ribozyme_mechanism.png/330px-Ribozyme_mechanism.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/8/8a/Ribozyme_mechanism.png/440px-Ribozyme_mechanism.png 2x" data-class="mw-file-element"> </a><figcaption>General mechanism utilized by ribozymes to cleave RNA molecules</figcaption></figure> <a href="/wiki/Ribozymes" class="mw-redirect" title="Ribozymes">Ribozymes</a> are catalytic RNA molecules used to inhibit <a href="/wiki/Gene_expression" title="Gene expression">gene expression</a>. These molecules work by cleaving <a href="/wiki/MRNA" class="mw-redirect" title="MRNA">mRNA</a> molecules, essentially silencing the genes that produced them. <a href="/wiki/Sidney_Altman" title="Sidney Altman">Sidney Altman</a> and <a href="/wiki/Thomas_Cech" title="Thomas Cech">Thomas Cech</a> first discovered catalytic RNA molecules, RNase P and group II intron ribozymes, in 1989 and won the Nobel Prize for their discovery.<a href="#cite_note-phyl-8">[8]</a><a href="#cite_note-9">[9]</a> Several types of ribozyme motifs exist, including <a href="/wiki/Hammerhead_ribozyme" title="Hammerhead ribozyme">hammerhead</a>, <a href="/wiki/Hairpin_ribozyme" title="Hairpin ribozyme">hairpin</a>, <a href="/wiki/Hepatitis_delta_virus_ribozyme" title="Hepatitis delta virus ribozyme">hepatitis delta virus</a>, <a href="/wiki/Group_I_intron" class="mw-redirect" title="Group I intron">group I</a>, <a href="/wiki/Group_II_intron" title="Group II intron">group II</a>, and <a href="/wiki/RNase_P" class="mw-redirect" title="RNase P">RNase P</a> ribozymes. Hammerhead, hairpin, and hepatitis delta virus (HDV) ribozyme motifs are generally found in <a href="/wiki/Viruses" class="mw-redirect" title="Viruses">viruses</a> or viroid RNAs.<a href="#cite_note-phyl-8">[8]</a> These motifs are able to self-cleave a specific phosphodiester bond on an mRNA molecule.<a href="#cite_note-phyl-8">[8]</a> Lower <a href="/wiki/Eukaryotes" class="mw-redirect" title="Eukaryotes">eukaryotes</a> and a few <a href="/wiki/Bacteria" title="Bacteria">bacteria</a> contain group I and group II ribozymes.<a href="#cite_note-phyl-8">[8]</a> These motifs can self-splice by cleaving and joining phosphodiester bonds.<a href="#cite_note-phyl-8">[8]</a> The last ribozyme motif, the RNase P ribozyme, is found in <a href="/wiki/Escherichia_coli" title="Escherichia coli">Escherichia coli</a> and is known for its ability to cleave the phosphodiester bonds of several <a href="/wiki/TRNA" class="mw-redirect" title="TRNA">tRNA</a> precursors when joined to a protein cofactor.<a href="#cite_note-phyl-8">[8]</a> The general <a href="/wiki/Catalytic_mechanism" class="mw-redirect" title="Catalytic mechanism">catalytic mechanism</a> used by ribozymes is similar to the mechanism used by protein <a href="/wiki/Ribonucleases" class="mw-redirect" title="Ribonucleases">ribonucleases</a>.<a href="#cite_note-doherty-10">[10]</a> These catalytic RNA molecules bind to a specific site and attack the neighboring phosphate in the RNA backbone with their 2' oxygen, which acts as a <a href="/wiki/Nucleophile" title="Nucleophile">nucleophile</a>, resulting in the formation of cleaved products with a 2'3'-cyclic phosphate and a 5' hydroxyl terminal end.<a href="#cite_note-doherty-10">[10]</a> This catalytic mechanism has been increasingly used by scientists to perform sequence-specific cleavage of target mRNA molecules. In addition, attempts are being made to use ribozymes to produce gene silencing therapeutics, which would silence genes that are responsible for causing diseases.<a href="#cite_note-Tollef-11">[11]</a> <div class="mw-heading mw-heading3"><h3 id="RNA_interference">RNA interference</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=8" title="Edit section: RNA interference" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <figure class="mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:RNAi-simplified.png" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f0/RNAi-simplified.png/330px-RNAi-simplified.png" decoding="async" width="330" height="282" class="mw-file-element" data-file-width="800" data-file-height="684"></noscript><span class="lazy-image-placeholder" style="width: 330px;height: 282px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f0/RNAi-simplified.png/330px-RNAi-simplified.png" data-width="330" data-height="282" data-mw-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f0/RNAi-simplified.png/495px-RNAi-simplified.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f0/RNAi-simplified.png/660px-RNAi-simplified.png 2x" data-class="mw-file-element"> </a><figcaption>Left:Overview of RNA interference.</figcaption></figure> RNA interference (<a href="/wiki/RNA_interference" title="RNA interference">RNAi</a>) is a natural process used by cells to regulate gene expression. It was discovered in 1998 by <a href="/wiki/Andrew_Fire" title="Andrew Fire">Andrew Fire</a> and <a href="/wiki/Craig_Mello" title="Craig Mello">Craig Mello</a>, who won the Nobel Prize for their discovery in 2006.<a href="#cite_note-NIH-12">[12]</a> The process to silence genes first begins with the entrance of a <a href="/wiki/DsRNA" class="mw-redirect" title="DsRNA">double-stranded RNA (dsRNA)</a> molecule into the cell, which triggers the RNAi pathway.<a href="#cite_note-NIH-12">[12]</a> The double-stranded molecule is then cut into small double-stranded fragments by an enzyme called <a href="/wiki/Dicer" title="Dicer">Dicer</a>.<a href="#cite_note-NIH-12">[12]</a> These small fragments, which include <a href="/wiki/RNA-induced_silencing_complex" title="RNA-induced silencing complex">small interfering RNAs (siRNA)</a> and <a href="/wiki/MiRNA" class="mw-redirect" title="MiRNA">microRNA (miRNA)</a>, are approximately 21–23 nucleotides in length.<a href="#cite_note-NIH-12">[12]</a><a href="#cite_note-Wilson-13">[13]</a> The fragments integrate into a multi-subunit protein called the <a href="/wiki/RNA-induced_silencing_complex" title="RNA-induced silencing complex">RNA-induced silencing complex</a>, which contains <a href="/wiki/Argonaute" title="Argonaute">Argonaute</a> proteins that are essential components of the RNAi pathway.<a href="#cite_note-NIH-12">[12]</a><a href="#cite_note-Wilson-13">[13]</a> One strand of the molecule, called the "guide" strand, binds to RISC, while the other strand, known as the "passenger" strand is degraded.<a href="#cite_note-NIH-12">[12]</a><a href="#cite_note-Wilson-13">[13]</a> The guide or antisense strand of the fragment that remains bound to RISC directs the sequence-specific silencing of the target mRNA molecule.<a href="#cite_note-Wilson-13">[13]</a> The genes can be silenced by siRNA molecules that cause the endonucleatic cleavage of the target mRNA molecules or by miRNA molecules that suppress translation of the mRNA molecule.<a href="#cite_note-Wilson-13">[13]</a> With the cleavage or translational repression of the mRNA molecules, the genes that form them are rendered essentially inactive.<a href="#cite_note-NIH-12">[12]</a> RNAi is thought to have evolved as a cellular defense mechanism against invaders, such as <a href="/wiki/RNA_viruses" class="mw-redirect" title="RNA viruses">RNA viruses</a>, or to combat the proliferation of <a href="/wiki/Transposons" class="mw-redirect" title="Transposons">transposons</a> within a cell's DNA.<a href="#cite_note-NIH-12">[12]</a> Both RNA viruses and transposons can exist as double-stranded RNA and lead to the activation of RNAi.<a href="#cite_note-NIH-12">[12]</a> Currently, <a href="/wiki/Small_interfering_RNA" title="Small interfering RNA">siRNAs</a> are being widely used to suppress specific <a href="/wiki/Gene_expression" title="Gene expression">gene expression</a> and to assess the function of <a href="/wiki/Gene" title="Gene">genes</a>. Companies utilizing this approach include <a href="/wiki/Alnylam_Pharmaceuticals" title="Alnylam Pharmaceuticals">Alnylam</a>, <a href="/wiki/Sanofi" title="Sanofi">Sanofi</a>,<a href="#cite_note-14">[14]</a> Arrowhead, Discerna,<a href="#cite_note-15">[15]</a> and <a href="/wiki/Persomics" title="Persomics">Persomics</a>,<a href="#cite_note-16">[16]</a> among others. <div class="mw-heading mw-heading3"><h3 id="Three_prime_untranslated_regions_and_microRNAs">Three prime untranslated regions and microRNAs</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=9" title="Edit section: Three prime untranslated regions and microRNAs" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Three_prime_untranslated_region" title="Three prime untranslated region">Three prime untranslated region</a></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/MicroRNA" title="MicroRNA">MicroRNA</a></div> The <a href="/wiki/Three_prime_untranslated_region" title="Three prime untranslated region">three prime untranslated regions</a> (3'UTRs) of <a href="/wiki/Messenger_RNA" title="Messenger RNA">messenger RNAs</a> (mRNAs) often contain regulatory sequences that post-transcriptionally cause gene silencing. Such 3'-UTRs often contain both <a href="/wiki/Binding_sites" class="mw-redirect" title="Binding sites">binding sites</a> for microRNAs (miRNAs) as well as for <a href="/wiki/Regulatory_protein" class="mw-redirect" title="Regulatory protein">regulatory proteins</a>. By binding to specific sites within the 3'-UTR, a large number of specific miRNAs decrease <a href="/wiki/Gene_expression" title="Gene expression">gene expression</a> of their particular target mRNAs by either inhibiting <a href="/wiki/Translation_(biology)" title="Translation (biology)">translation</a> or directly causing degradation of the transcript, using a mechanism similar to RNA interference (see <a href="/wiki/MicroRNA" title="MicroRNA">MicroRNA</a>). The 3'-UTR also may have silencer regions that bind repressor proteins that inhibit the expression of an mRNA.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] The 3'-UTR often contains <a href="/wiki/Three_prime_untranslated_region#MicroRNA_response_elements" title="Three prime untranslated region">microRNA response elements (MREs)</a>. MREs are sequences to which miRNAs bind and cause gene silencing. These are prevalent motifs within 3'-UTRs. Among all regulatory motifs within the 3'-UTRs (e.g. including silencer regions), MREs make up about half of the motifs.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] As of 2014, the <a href="/wiki/MiRBase" title="MiRBase">miRBase</a> web site,<a href="#cite_note-17">[17]</a> an archive of miRNA <a href="/wiki/Sequence_(biology)" title="Sequence (biology)">sequences</a> and annotations, listed 28,645 entries in 233 biologic species. Of these, 1,881 miRNAs were in annotated human miRNA loci. miRNAs were predicted to each have an average of about four hundred target mRNAs (causing gene silencing of several hundred genes).<a href="#cite_note-Freidman-18">[18]</a> Freidman et al.<a href="#cite_note-Freidman-18">[18]</a> estimate that >45,000 miRNA <a href="/wiki/Biological_target" title="Biological target">target sites</a> within human mRNA 3'UTRs are conserved above background levels, and >60% of human protein-coding <a href="/wiki/Genes" class="mw-redirect" title="Genes">genes</a> have been under selective pressure to maintain pairing to miRNAs.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] Direct experiments show that a single miRNA can reduce the stability of hundreds of unique mRNAs.<a href="#cite_note-pmid15685193-19">[19]</a> Other experiments show that a single <a href="/wiki/Micro_RNA" class="mw-redirect" title="Micro RNA">miRNA</a> may repress the production of hundreds of proteins, but that this repression often is relatively mild (less than 2-fold).<a href="#cite_note-20">[20]</a><a href="#cite_note-21">[21]</a> The effects of miRNA dysregulation of gene expression seem to be important in cancer.<a href="#cite_note-pmid21931505-22">[22]</a> For instance, in gastrointestinal cancers, nine miRNAs have been identified as <a href="/wiki/Epigenetics" title="Epigenetics">epigenetically</a> altered and effective in down regulating DNA repair enzymes.<a href="#cite_note-pmid25987950-23">[23]</a> The effects of miRNA dysregulation of gene expression also seem to be important in <a href="/wiki/Neuropsychiatric" class="mw-redirect" title="Neuropsychiatric">neuropsychiatric</a> disorders, such as schizophrenia, bipolar disorder, major depression, Parkinson's disease, Alzheimer's disease and autism spectrum disorders.<a href="#cite_note-pmid24653674-24">[24]</a><a href="#cite_note-pmid22539927-25">[25]</a><a href="#cite_note-pmid25636176-26">[26]</a> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(3)"><h2 id="Applications">Applications</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=10" title="Edit section: Applications" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-3 collapsible-block" id="mf-section-3"> <div class="mw-heading mw-heading3"><h3 id="Medical_research">Medical research</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=11" title="Edit section: Medical research" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> Gene silencing techniques have been widely used by researchers to study genes associated with disorders. These disorders include <a href="/wiki/Cancer" title="Cancer">cancer</a>, <a href="/wiki/Infectious_diseases" class="mw-redirect" title="Infectious diseases">infectious diseases</a>, <a href="/wiki/Respiratory_diseases" class="mw-redirect" title="Respiratory diseases">respiratory diseases</a>, and <a href="/wiki/Neurodegenerative_disorders" class="mw-redirect" title="Neurodegenerative disorders">neurodegenerative disorders</a>. Gene silencing is also currently being used in drug discovery efforts, such as <a href="/wiki/Synthetic_lethality" title="Synthetic lethality">synthetic lethality</a>, <a href="/wiki/High-throughput_screening" title="High-throughput screening">high-throughput screening</a>, and miniaturized RNAi screens.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] <div class="mw-heading mw-heading4"><h4 id="Cancer">Cancer</h4> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=12" title="Edit section: Cancer" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <a href="/wiki/RNA_interference" title="RNA interference">RNA interference</a> has been used to silence genes associated with several cancers. In <a href="/wiki/In_vitro" title="In vitro">in vitro</a> studies of <a href="/wiki/Chronic_myelogenous_leukemia" title="Chronic myelogenous leukemia">chronic myelogenous leukemia (CML)</a>, <a href="/wiki/SiRNA" class="mw-redirect" title="SiRNA">siRNA</a> was used to cleave the fusion protein, <a href="/wiki/BCR-ABL" class="mw-redirect" title="BCR-ABL">BCR-ABL</a>, which prevents the drug <a href="/wiki/Gleevec" class="mw-redirect" title="Gleevec">Gleevec</a> (<a href="/wiki/Imatinib" title="Imatinib">imatinib</a>) from binding to the cancer cells.<a href="#cite_note-Chen-27">[27]</a> Cleaving the fusion protein reduced the amount of transformed <a href="/wiki/Hematopoietic" class="mw-redirect" title="Hematopoietic">hematopoietic</a> cells that spread throughout the body by increasing the sensitivity of the cells to the drug.<a href="#cite_note-Chen-27">[27]</a> RNA interference can also be used to target specific mutants. For instance, siRNAs were able to bind specifically to tumor suppressor <a href="/wiki/P53" title="P53">p53</a> molecules containing a single <a href="/wiki/Point_mutation" title="Point mutation">point mutation</a> and destroy it, while leaving the wild-type suppressor intact.<a href="#cite_note-28">[28]</a> Receptors involved in <a href="/wiki/Mitogenic" class="mw-redirect" title="Mitogenic">mitogenic</a> pathways that lead to the increased production of cancer cells there have also been targeted by siRNA molecules. The <a href="/wiki/CXCR4" title="CXCR4">chemokine receptor chemokine receptor 4 (CXCR4)</a>, associated with the proliferation of breast cancer, was cleaved by siRNA molecules that reduced the number of divisions commonly observed by the cancer cells.<a href="#cite_note-29">[29]</a> Researchers have also used siRNAs to selectively regulate the expression of cancer-related genes. Antiapoptotic proteins, such as <a href="/wiki/Clusterin" title="Clusterin">clusterin</a> and <a href="/wiki/Survivin" title="Survivin">survivin</a>, are often expressed in cancer cells.<a href="#cite_note-July-30">[30]</a><a href="#cite_note-Ning-31">[31]</a> Clusterin and survivin-targeting siRNAs were used to reduce the number of antiapoptotic proteins and, thus, increase the sensitivity of the cancer cells to chemotherapy treatments.<a href="#cite_note-July-30">[30]</a><a href="#cite_note-Ning-31">[31]</a> <a href="/wiki/In_vivo" title="In vivo">In vivo</a> studies are also being increasingly utilized to study the potential use of siRNA molecules in cancer therapeutics. For instance, mice implanted with <a href="/wiki/Colon_adenocarcinoma" class="mw-redirect" title="Colon adenocarcinoma">colon adenocarcinoma</a> cells were found to survive longer when the cells were pretreated with siRNAs that targeted <a href="/wiki/B-catenin" class="mw-redirect" title="B-catenin">B-catenin</a> in the cancer cells.<a href="#cite_note-32">[32]</a> <div class="mw-heading mw-heading4"><h4 id="Infectious_disease">Infectious disease</h4> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=13" title="Edit section: Infectious disease" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <div class="mw-heading mw-heading5"><h5 id="Viruses">Viruses</h5> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=14" title="Edit section: Viruses" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> Viral genes and host genes that are required for viruses to replicate or enter the cell, or that play an important role in the life cycle of the virus are often targeted by antiviral therapies. RNAi has been used to target genes in several viral diseases, such as the <a href="/wiki/Human_immunodeficiency_virus" class="mw-redirect" title="Human immunodeficiency virus">human immunodeficiency virus (HIV)</a> and <a href="/wiki/Hepatitis" title="Hepatitis">hepatitis</a>.<a href="#cite_note-Dave-33">[33]</a><a href="#cite_note-wilson-34">[34]</a> In particular, siRNA was used to silence the primary HIV receptor chemokine receptor 5 (CCR5).<a href="#cite_note-Qin-35">[35]</a> This prevented the virus from entering the human peripheral blood lymphocytes and the primary hematopoietic stem cells.<a href="#cite_note-Qin-35">[35]</a><a href="#cite_note-li-36">[36]</a> A similar technique was used to decrease the amount of the detectable virus in <a href="/wiki/Hepatitis_B" title="Hepatitis B">hepatitis B</a> and C infected cells. In hepatitis B, siRNA silencing was used to target the surface antigen on the hepatitis B virus and led to a decrease in the number of viral components.<a href="#cite_note-giladi-37">[37]</a> In addition, siRNA techniques used in hepatitis C were able to lower the amount of the virus in the cell by 98%.<a href="#cite_note-randall_2003-38">[38]</a><a href="#cite_note-randall_2004-39">[39]</a> RNA interference has been in commercial use to control virus diseases of plants for over 20 years (see <a href="/wiki/Plant_disease_resistance" title="Plant disease resistance">Plant disease resistance</a>). In 1986–1990, multiple examples of "coat protein-mediated resistance" against plant viruses were published, before RNAi had been discovered.<a href="#cite_note-40">[40]</a> In 1993, work with tobacco etch virus first demonstrated that host organisms can target specific virus or mRNA sequences for degradation, and that this activity is the mechanism behind some examples of virus resistance in transgenic plants.<a href="#cite_note-41">[41]</a><a href="#cite_note-42">[42]</a> The discovery of small interfering RNAs (the specificity determinant in RNA-mediated gene silencing) also utilized virus-induced post-transcriptional gene silencing in plants.<a href="#cite_note-43">[43]</a> By 1994, transgenic squash varieties had been generated expressing coat protein genes from three different viruses, providing squash hybrids with field-validated multiviral resistance that remain in commercial use at present. Potato lines expressing viral replicase sequences that confer resistance to potato leafroll virus were sold under the trade names NewLeaf Y and NewLeaf Plus, and were widely accepted in commercial production in 1999–2001, until McDonald's Corp. decided not to purchase <a href="/wiki/Genetically_modified_food" title="Genetically modified food">GM</a> potatoes and Monsanto decided to close their NatureMark potato business.<a href="#cite_note-Kaniewski_reference-44">[44]</a> Another frequently cited example of virus resistance mediated by gene silencing involves papaya, where the Hawaiian papaya industry was rescued by virus-resistant GM papayas produced and licensed by university researchers rather than a large corporation.<a href="#cite_note-45">[45]</a> These papayas also remain in use at present, although not without significant public protest,<a href="#cite_note-46">[46]</a><a href="#cite_note-47">[47]</a> which is notably less evident in medical uses of gene silencing. Gene silencing techniques have also been used to target other viruses, such as the <a href="/wiki/Human_papilloma_virus" class="mw-redirect" title="Human papilloma virus">human papilloma virus</a>, the <a href="/wiki/West_Nile_virus" title="West Nile virus">West Nile virus</a>, and the Tulane virus. The E6 gene in tumor samples retrieved from patients with the human papilloma virus was targeted and found to cause apoptosis in the infected cells.<a href="#cite_note-butz-48">[48]</a> Plasmid siRNA expression vectors used to target the West Nile virus were also able to prevent the replication of viruses in cell lines.<a href="#cite_note-49">[49]</a> In addition, siRNA has been found to be successful in preventing the replication of the Tulane virus, part of the virus family <a href="/wiki/Caliciviridae" title="Caliciviridae">Caliciviridae</a>, by targeting both its structural and non-structural genes.<a href="#cite_note-Tulane-50">[50]</a> By targeting the NTPase gene, one dose of siRNA 4 hours pre-infection was shown to control Tulane virus replication for 48 hours post-infection, reducing the viral <a href="/wiki/Titer" title="Titer">titer</a> by up to 2.6 logarithms.<a href="#cite_note-Tulane-50">[50]</a> Although the Tulane virus is species-specific and does not affect humans, it has been shown to be closely related to the human <a href="/wiki/Norovirus" title="Norovirus">norovirus</a>, which is the most common cause of <a href="/wiki/Acute_gastroenteritis" class="mw-redirect" title="Acute gastroenteritis">acute gastroenteritis</a> and <a href="/wiki/Food-borne_disease" class="mw-redirect" title="Food-borne disease">food-borne disease</a> outbreaks in the United States.<a href="#cite_note-CDC_Norovirus-51">[51]</a> Human noroviruses are notorious for being difficult to study in the laboratory, but the Tulane virus offers a model through which to study this family of viruses for the clinical goal of developing therapies that can be used to treat illnesses caused by human norovirus.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] <div class="mw-heading mw-heading5"><h5 id="Bacteria">Bacteria</h5> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=15" title="Edit section: Bacteria" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Prokaryote_cell.svg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c5/Prokaryote_cell.svg/220px-Prokaryote_cell.svg.png" decoding="async" width="220" height="247" class="mw-file-element" data-file-width="910" data-file-height="1020"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 247px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c5/Prokaryote_cell.svg/220px-Prokaryote_cell.svg.png" data-width="220" data-height="247" data-mw-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/c5/Prokaryote_cell.svg/330px-Prokaryote_cell.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/c5/Prokaryote_cell.svg/440px-Prokaryote_cell.svg.png 2x" data-class="mw-file-element"> </a><figcaption>Structure of a typical Gram-positive bacterial cell</figcaption></figure> Unlike viruses, bacteria are not as susceptible to silencing by siRNA.<a href="#cite_note-Lieberman-52">[52]</a> This is largely due to how bacteria replicate. Bacteria replicate outside of the host cell and do not contain the necessary machinery for RNAi to function.<a href="#cite_note-Lieberman-52">[52]</a> However, bacterial infections can still be suppressed by siRNA by targeting the host genes that are involved in the immune response caused by the infection or by targeting the host genes involved in mediating the entry of bacteria into cells.<a href="#cite_note-Lieberman-52">[52]</a><a href="#cite_note-leung-53">[53]</a> For instance, siRNA was used to reduce the amount of pro-inflammatory <a href="/wiki/Cytokines" class="mw-redirect" title="Cytokines">cytokines</a> expressed in the cells of mice treated with <a href="/wiki/Lipopolysaccharide" title="Lipopolysaccharide">lipopolysaccharide (LPS)</a>.<a href="#cite_note-Lieberman-52">[52]</a><a href="#cite_note-sorensen-54">[54]</a> The reduced expression of the inflammatory cytokine, <a href="/wiki/Tumor_necrosis_factor_%CE%B1" class="mw-redirect" title="Tumor necrosis factor α">tumor necrosis factor α (TNFα)</a>, in turn, caused a reduction in the septic shock felt by the LPS-treated mice.<a href="#cite_note-sorensen-54">[54]</a> In addition, siRNA was used to prevent the bacteria, Psueomonas aeruginosa, from invading murine lung epithelial cells by knocking down the caveolin-2 (CAV2) gene.<a href="#cite_note-55">[55]</a> Thus, though bacteria cannot be directly targeted by siRNA mechanisms, they can still be affected by siRNA when the components involved in the bacterial infection are targeted.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] <div class="mw-heading mw-heading4"><h4 id="Respiratory_diseases">Respiratory diseases</h4> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=16" title="Edit section: Respiratory diseases" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> Ribozymes, antisense oligonucleotides, and more recently RNAi have been used to target mRNA molecules involved in <a href="/wiki/Asthma" title="Asthma">asthma</a>.<a href="#cite_note-leung-53">[53]</a><a href="#cite_note-Popescu-56">[56]</a> These experiments have suggested that siRNA may be used to combat other respiratory diseases, such as <a href="/wiki/Chronic_obstructive_pulmonary_disease" title="Chronic obstructive pulmonary disease">chronic obstructive pulmonary disease (COPD)</a> and <a href="/wiki/Cystic_fibrosis" title="Cystic fibrosis">cystic fibrosis</a>.<a href="#cite_note-leung-53">[53]</a> COPD is characterized by <a href="/wiki/Goblet_cell" title="Goblet cell">goblet cell</a> <a href="/wiki/Hyperplasia" title="Hyperplasia">hyperplasia</a> and <a href="/wiki/Mucus" title="Mucus">mucus</a> <a href="/wiki/Hypersecretion" class="mw-redirect" title="Hypersecretion">hypersecretion</a>.<a href="#cite_note-Pistelli-57">[57]</a> Mucus secretion was found to be reduced when the <a href="/wiki/Transforming_growth_factor_alpha" class="mw-redirect" title="Transforming growth factor alpha">transforming growth factor (TGF)-α</a> was targeted by siRNA in NCI-H292 human airway <a href="/wiki/Epithelial_cells" class="mw-redirect" title="Epithelial cells">epithelial cells</a>.<a href="#cite_note-58">[58]</a> In addition to mucus hypersecretion, <a href="/wiki/Chronic_inflammation" class="mw-redirect" title="Chronic inflammation">chronic inflammation</a> and damaged lung tissue are characteristic of COPD and asthma. The <a href="/wiki/Transforming_growth_factor_beta" title="Transforming growth factor beta">transforming growth factor TGF-β</a> is thought to play a role in these manifestations.<a href="#cite_note-rennard-59">[59]</a><a href="#cite_note-sacco-60">[60]</a> As a result, when <a href="/wiki/Interferon_gamma" title="Interferon gamma">interferon (IFN)-γ</a> was used to knock down TGF-β, <a href="/wiki/Pulmonary_fibrosis" title="Pulmonary fibrosis">fibrosis</a> of the lungs, caused by damage and scarring to lung tissue, was improved.<a href="#cite_note-61">[61]</a><a href="#cite_note-62">[62]</a> <div class="mw-heading mw-heading4"><h4 id="Neurodegenerative_disorders">Neurodegenerative disorders</h4> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=17" title="Edit section: Neurodegenerative disorders" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <div class="mw-heading mw-heading5"><h5 id="Huntington's_disease">Huntington's disease</h5> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=18" title="Edit section: Huntington's disease" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:PDB_3io4_EBI.png" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/6f/PDB_3io4_EBI.png/220px-PDB_3io4_EBI.png" decoding="async" width="220" height="165" class="mw-file-element" data-file-width="800" data-file-height="600"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 165px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/6/6f/PDB_3io4_EBI.png/220px-PDB_3io4_EBI.png" data-width="220" data-height="165" data-mw-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/6f/PDB_3io4_EBI.png/330px-PDB_3io4_EBI.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/6f/PDB_3io4_EBI.png/440px-PDB_3io4_EBI.png 2x" data-class="mw-file-element"> </a><figcaption>Crystallographic structure of the N-terminal region of the human huntingtin protein.</figcaption></figure> <a href="/wiki/Huntington%27s_disease" title="Huntington's disease">Huntington's disease (HD)</a> results from a mutation in the <a href="/wiki/Huntingtin_gene" class="mw-redirect" title="Huntingtin gene">huntingtin gene</a> that causes an excess of CAG repeats.<a href="#cite_note-stanford-63">[63]</a> The gene then forms a mutated <a href="/wiki/Huntingtin_protein" class="mw-redirect" title="Huntingtin protein">huntingtin protein</a> with polyglutamine repeats near the <a href="/wiki/Amino_terminus" class="mw-redirect" title="Amino terminus">amino terminus</a>.<a href="#cite_note-mantha-64">[64]</a> This disease is incurable and known to cause motor, <a href="/wiki/Cognitive_deficit" class="mw-redirect" title="Cognitive deficit">cognitive</a>, and behavioral deficits.<a href="#cite_note-harper-65">[65]</a> Researchers have been looking to gene silencing as a potential therapeutic for HD.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] Gene silencing can be used to treat HD by targeting the mutant huntingtin protein. The mutant huntingtin protein has been targeted through gene silencing that is allele specific using <a href="/wiki/Allele_specific_oligonucleotides" class="mw-redirect" title="Allele specific oligonucleotides">allele specific oligonucleotides</a>. In this method, the antisense oligonucleotides are used to target <a href="/wiki/Single-nucleotide_polymorphism" title="Single-nucleotide polymorphism">single nucleotide polymorphism (SNPs)</a>, which are single nucleotide changes in the DNA sequence, since HD patients have been found to share common SNPs that are associated with the mutated huntingtin allele. It has been found that approximately 85% of patients with HD can be covered when three SNPs are targeted. In addition, when antisense oligonucleotides were used to target an HD-associated SNP in mice, there was a 50% decrease in the mutant huntingtin protein.<a href="#cite_note-stanford-63">[63]</a> Non-allele specific gene silencing using siRNA molecules has also been used to silence the mutant huntingtin proteins. Through this approach, instead of targeting SNPs on the mutated protein, all of the normal and mutated huntingtin proteins are targeted. When studied in mice, it was found that siRNA could reduce the normal and mutant huntingtin levels by 75%. At this level, they found that the mice developed improved <a href="/wiki/Motor_control" title="Motor control">motor control</a> and a longer <a href="/wiki/Survival_rate" title="Survival rate">survival rate</a> when compared to the controls.<a href="#cite_note-stanford-63">[63]</a> Thus, gene silencing methods may prove to be beneficial in treating HD. <div class="mw-heading mw-heading5"><h5 id="Amyotrophic_lateral_sclerosis">Amyotrophic lateral sclerosis</h5> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=19" title="Edit section: Amyotrophic lateral sclerosis" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <a href="/wiki/Amyotrophic_lateral_sclerosis" class="mw-redirect" title="Amyotrophic lateral sclerosis">Amyotrophic lateral sclerosis (ALS)</a>, also called Lou Gehrig's disease, is a <a href="/wiki/Motor_neuron_disease" class="mw-redirect" title="Motor neuron disease">motor neuron disease</a> that affects the <a href="/wiki/Brain" title="Brain">brain</a> and <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a>. The disease causes <a href="/wiki/Motor_neurons" class="mw-redirect" title="Motor neurons">motor neurons</a> to degenerate, which eventually leads to neuron death and muscular degeneration.<a href="#cite_note-ALS-66">[66]</a> Hundreds of mutations in the Cu/Zn <a href="/wiki/Superoxide_dismutase" title="Superoxide dismutase">superoxide dismutase</a> (SOD1) gene have been found to cause ALS.<a href="#cite_note-Geng-67">[67]</a> Gene silencing has been used to knock down the SOD1 mutant that is characteristic of ALS.<a href="#cite_note-Geng-67">[67]</a><a href="#cite_note-68">[68]</a> In specific, siRNA molecules have been successfully used to target the SOD1 mutant gene and reduce its expression through allele-specific gene silencing.<a href="#cite_note-Geng-67">[67]</a><a href="#cite_note-ding-69">[69]</a> <div class="mw-heading mw-heading4"><h4 id="Therapeutics_challenges">Therapeutics challenges</h4> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=20" title="Edit section: Therapeutics challenges" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Lentiviral_vector.png" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/95/Lentiviral_vector.png/220px-Lentiviral_vector.png" decoding="async" width="220" height="107" class="mw-file-element" data-file-width="961" data-file-height="467"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 107px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/9/95/Lentiviral_vector.png/220px-Lentiviral_vector.png" data-width="220" data-height="107" data-mw-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/95/Lentiviral_vector.png/330px-Lentiviral_vector.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/95/Lentiviral_vector.png/440px-Lentiviral_vector.png 2x" data-class="mw-file-element"> </a><figcaption>Basic mechanism used by viral vectors to deliver genes to target cells. Example shown is a lentiviral vector.</figcaption></figure> There are several challenges associated with gene silencing therapies, including <a href="/wiki/Gene_delivery" title="Gene delivery">delivery</a> and specificity for targeted cells. For instance, for treatment of neurodegenerative disorders, molecules for a prospective gene silencing therapy must be delivered to the brain. The <a href="/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier">blood–brain barrier</a> makes it difficult to deliver molecules into the brain through the bloodstream by preventing the passage of the majority of molecules that are injected or absorbed into the blood.<a href="#cite_note-stanford-63">[63]</a><a href="#cite_note-mantha-64">[64]</a> Thus, researchers have found that they must directly inject the molecules or implant pumps that push them into the brain.<a href="#cite_note-stanford-63">[63]</a> Once inside the brain, however, the molecules must move inside of the targeted cells. In order to efficiently deliver siRNA molecules into the cells, <a href="/wiki/Viral_vectors" class="mw-redirect" title="Viral vectors">viral vectors</a> can be used.<a href="#cite_note-stanford-63">[63]</a><a href="#cite_note-harper-65">[65]</a> Nevertheless, this method of delivery can also be problematic as it can elicit an immune response against the molecules. In addition to delivery, specificity has also been found to be an issue in gene silencing. Both antisense oligonucleotides and siRNA molecules can potentially bind to the wrong mRNA molecule.<a href="#cite_note-stanford-63">[63]</a> Thus, researchers are searching for more efficient methods to deliver and develop specific gene silencing therapeutics that are still safe and effective.[<a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a>] <div class="mw-heading mw-heading3"><h3 id="Food">Food</h3> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=21" title="Edit section: Food" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Arctic_Apples" title="Arctic Apples">Arctic Apples</a></div> Arctic Apples are a suite of trademarked<a href="#cite_note-70">[70]</a> apples that contain a nonbrowning trait created by using gene silencing to reduce the expression of polyphenol oxidase (PPO). It is the first approved food product to use this technique.<a href="#cite_note-71">[71]</a> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(4)"><h2 id="See_also">See also</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=22" title="Edit section: See also" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-4 collapsible-block" id="mf-section-4"> <ul><li><a href="/wiki/CRISPR" title="CRISPR">CRISPR</a></li> <li><a href="/wiki/DNA-directed_RNA_interference" title="DNA-directed RNA interference">DNA-directed RNA interference</a></li> <li><a href="/wiki/Gene_drive" title="Gene drive">Gene drive</a></li> <li><a href="/wiki/Gene_knockdown" title="Gene knockdown">Gene knockdown</a></li> <li><a href="/wiki/Polypurine_Reverse-Hoogsteen_hairpins" class="mw-redirect" title="Polypurine Reverse-Hoogsteen hairpins">PPRHs</a></li></ul> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(5)"><h2 id="References">References</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=23" title="Edit section: References" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-5 collapsible-block" id="mf-section-5"> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width reflist-columns-2"> <ol class="references"> <li id="cite_note-redberry-1">^ <a href="#cite_ref-redberry_1-0">a</a> <a href="#cite_ref-redberry_1-1">b</a> <style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFRedberry2006" class="citation book cs1">Redberry, Grace (2006). Gene silencing : new research. New York: Nova Science Publishers. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/9781594548321" title="Special:BookSources/9781594548321"><bdi>9781594548321</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Gene+silencing+%3A+new+research&rft.place=New+York&rft.pub=Nova+Science+Publishers&rft.date=2006&rft.isbn=9781594548321&rft.aulast=Redberry&rft.aufirst=Grace&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGene+silencing" class="Z3988"> </li> <li id="cite_note-NCBI-2">^ <a href="#cite_ref-NCBI_2-0">a</a> <a href="#cite_ref-NCBI_2-1">b</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/genome/probe/doc/ApplSilencing.shtml">"Gene Silencing"</a>. 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Acta Pharmacologica Sinica. 29 (2): 211–6. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1745-7254.2008.00740.x">10.1111/j.1745-7254.2008.00740.x</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18215350">18215350</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:24809180">24809180</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Acta+Pharmacologica+Sinica&rft.atitle=Double-mismatched+siRNAs+enhance+selective+gene+silencing+of+a+mutant+ALS-causing+allele&rft.volume=29&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E211-%3C%2Fspan%3E6&rft.date=2008-02&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A24809180%23id-name%3DS2CID&rft_id=info%3Apmid%2F18215350&rft_id=info%3Adoi%2F10.1111%2Fj.1745-7254.2008.00740.x&rft.aulast=Geng&rft.aufirst=CM&rft.au=Ding%2C+HL&rft_id=https%3A%2F%2Fdoi.org%2F10.1111%252Fj.1745-7254.2008.00740.x&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGene+silencing" class="Z3988"> </li> <li id="cite_note-68"><a href="#cite_ref-68">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBoulis" class="citation web cs1">Boulis, Nicholas. <a rel="nofollow" class="external text" href="http://www.sfn.org/~/media/SfN/Documents/Short%20Courses/2011%20Short%20Course%20I/2011_SC1_Boulis.ashx">"Gene Therapy for Motor Neuron Disease"</a>. Society for Neuroscience. Retrieved 13 December 2013.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Gene+Therapy+for+Motor+Neuron+Disease&rft.pub=Society+for+Neuroscience&rft.aulast=Boulis&rft.aufirst=Nicholas&rft_id=http%3A%2F%2Fwww.sfn.org%2F~%2Fmedia%2FSfN%2FDocuments%2FShort%2520Courses%2F2011%2520Short%2520Course%2520I%2F2011_SC1_Boulis.ashx&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGene+silencing" class="Z3988"> </li> <li id="cite_note-ding-69"><a href="#cite_ref-ding_69-0">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDingSchwarzKeeneAffar_el2003" class="citation journal cs1">Ding H, Schwarz DS, Keene A, Affar el B, Fenton L, Xia X, Shi Y, Zamore PD, Xu Z (August 2003). "Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis". Aging Cell. 2 (4): 209–17. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1046%2Fj.1474-9728.2003.00054.x">10.1046/j.1474-9728.2003.00054.x</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12934714">12934714</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:31752201">31752201</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Aging+Cell&rft.atitle=Selective+silencing+by+RNAi+of+a+dominant+allele+that+causes+amyotrophic+lateral+sclerosis&rft.volume=2&rft.issue=4&rft.pages=%3Cspan+class%3D%22nowrap%22%3E209-%3C%2Fspan%3E17&rft.date=2003-08&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A31752201%23id-name%3DS2CID&rft_id=info%3Apmid%2F12934714&rft_id=info%3Adoi%2F10.1046%2Fj.1474-9728.2003.00054.x&rft.aulast=Ding&rft.aufirst=H&rft.au=Schwarz%2C+DS&rft.au=Keene%2C+A&rft.au=Affar+el%2C+B&rft.au=Fenton%2C+L&rft.au=Xia%2C+X&rft.au=Shi%2C+Y&rft.au=Zamore%2C+PD&rft.au=Xu%2C+Z&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGene+silencing" class="Z3988"> </li> <li id="cite_note-70"><a href="#cite_ref-70">^</a> <a rel="nofollow" class="external text" href="https://www.aphis.usda.gov/brs/aphisdocs/10_16101p.pdf">Petition for Determination of Nonregulated Status: Arctic™ Apple (Malus x domestica) Events GD743 and GS784</a>. United States Department of Agriculture – Animal and Plant Health Inspection Service. Retrieved 2012-08-03. </li> <li id="cite_note-71"><a href="#cite_ref-71">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://web.archive.org/web/20130925060233/http://www.arcticapples.com/arctic-apples-story/how-we-keep-apples-from-turning-brown">"Apple-to-apple transformation"</a>. Okanagan Specialty Fruits. Archived from <a rel="nofollow" class="external text" href="http://www.arcticapples.com/arctic-apples-story/how-we-keep-apples-from-turning-brown">the original</a> on 2013-09-25. Retrieved 2012-08-03.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=Okanagan+Specialty+Fruits&rft.atitle=Apple-to-apple+transformation&rft_id=http%3A%2F%2Fwww.arcticapples.com%2Farctic-apples-story%2Fhow-we-keep-apples-from-turning-brown&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGene+silencing" class="Z3988"> </li> </ol></div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(6)"><h2 id="External_links">External links</h2> <a role="button" href="/w/index.php?title=Gene_silencing&action=edit&section=24" title="Edit section: External links" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> edit </a> </div><section class="mf-section-6 collapsible-block" id="mf-section-6"> <ul><li><a rel="nofollow" class="external text" href="http://rnaiatlas.ethz.ch/">RNAiAtlas - database of siRNA libraries and their target analysis results</a><a rel="nofollow" class="external text" href="https://web.archive.org/web/20150210230607/http://rnaiatlas.ethz.ch/">Archived</a> February 10, 2015, at the <a href="/wiki/Wayback_Machine" title="Wayback Machine">Wayback Machine</a>.</li> <li><a rel="nofollow" class="external text" href="https://web.archive.org/web/20110721173426/http://www.gmo-safety.eu/database/1030.transgenic-apple-varieties-approaches-preventing-outcrossing-possible-effects-micro-organisms.html">Science project: Transgenic apple varieties</a> Approaches to preventing outcrossing – possible effects on micro-organisms</li> <li><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=Gene+silencing">Gene+silencing</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li> <li><a rel="nofollow" class="external text" href="https://web.archive.org/web/20080829180955/http://www.4engr.com/research/catalog/237/index.html">Research project: New Cost-effective method for gene silencing</a></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFvan_LeeuwenGottschling2002" class="citation book cs1">van Leeuwen F, Gottschling DE (2002). "Assays for gene silencing in yeast". Guide to Yeast Genetics and Molecular and Cell Biology - Part B. Methods in Enzymology. Vol. 350. pp. 165–86. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0076-6879%2802%2950962-9">10.1016/S0076-6879(02)50962-9</a>. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/9780121822538" title="Special:BookSources/9780121822538"><bdi>9780121822538</bdi></a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12073311">12073311</a>.</cite><span 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.navbar{float:left;text-align:left;margin-right:0.5em}body.skin--responsive .mw-parser-output .navbox-image img{max-width:none!important}@media print{body.ns-0 .mw-parser-output .navbox{display:none!important}}</style></div>    </section></div> <noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?useformat=mobile&type=1x1&usesul3=0" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Gene_silencing&oldid=1254907050">https://en.wikipedia.org/w/index.php?title=Gene_silencing&oldid=1254907050</a>"</div></div> </div> <div class="post-content" id="page-secondary-actions"> </div> </main> <footer class="mw-footer minerva-footer" role="contentinfo"> <a class="last-modified-bar" href="/w/index.php?title=Gene_silencing&action=history"> <div class="post-content last-modified-bar__content"> Last edited on 2 November 2024, at 07:37 </div> </a> <div class="post-content footer-content"> <div id='mw-data-after-content'> <div class="read-more-container"></div> </div> <div id="p-lang"> <h4>Languages</h4> <section> <ul id="p-variants" class="minerva-languages"></ul> <ul class="minerva-languages"><li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%A5%D8%B3%D9%83%D8%A7%D8%AA_%D8%A7%D9%84%D8%AC%D9%8A%D9%86" title="إسكات الجين – Arabic" lang="ar" hreflang="ar" data-title="إسكات الجين" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target">العربية</a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/Uti%C5%A1avanje_gena" title="Utišavanje gena – Bosnian" lang="bs" hreflang="bs" data-title="Utišavanje gena" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target">Bosanski</a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Silenciament_g%C3%A8nic" title="Silenciament gènic – Catalan" lang="ca" hreflang="ca" data-title="Silenciament gènic" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target">Català</a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Gen-Silencing" title="Gen-Silencing – German" lang="de" hreflang="de" data-title="Gen-Silencing" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target">Deutsch</a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Silenciamiento_g%C3%A9nico" title="Silenciamiento génico – Spanish" lang="es" hreflang="es" data-title="Silenciamiento génico" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target">Español</a></li><li class="interlanguage-link interwiki-eo mw-list-item"><a href="https://eo.wikipedia.org/wiki/Gen-silentigo" title="Gen-silentigo – Esperanto" lang="eo" hreflang="eo" data-title="Gen-silentigo" data-language-autonym="Esperanto" data-language-local-name="Esperanto" class="interlanguage-link-target">Esperanto</a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%AE%D8%A7%D9%85%D9%88%D8%B4%E2%80%8C%D8%B3%D8%A7%D8%B2%DB%8C_%DA%98%D9%86" title="خاموش‌سازی ژن – Persian" lang="fa" hreflang="fa" data-title="خاموش‌سازی ژن" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target">فارسی</a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Extinction_de_g%C3%A8ne" title="Extinction de gène – French" lang="fr" hreflang="fr" data-title="Extinction de gène" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target">Français</a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Peredaman_gen" title="Peredaman gen – Indonesian" lang="id" hreflang="id" data-title="Peredaman gen" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target">Bahasa Indonesia</a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%94%D7%A9%D7%AA%D7%A7%D7%AA_%D7%92%D7%A0%D7%99%D7%9D" title="השתקת גנים – Hebrew" lang="he" hreflang="he" data-title="השתקת גנים" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target">עברית</a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Penyenyapan_gen" title="Penyenyapan gen – Malay" lang="ms" hreflang="ms" data-title="Penyenyapan gen" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target">Bahasa Melayu</a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E9%81%BA%E4%BC%9D%E5%AD%90%E3%82%B5%E3%82%A4%E3%83%AC%E3%83%B3%E3%82%B7%E3%83%B3%E3%82%B0" title="遺伝子サイレンシング – Japanese" lang="ja" hreflang="ja" data-title="遺伝子サイレンシング" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target">日本語</a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Wyciszenie_genu" title="Wyciszenie genu – Polish" lang="pl" hreflang="pl" data-title="Wyciszenie genu" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target">Polski</a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Silenciamento_gen%C3%A9tico" title="Silenciamento genético – Portuguese" lang="pt" hreflang="pt" data-title="Silenciamento genético" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target">Português</a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%9F%D0%BE%D0%B4%D0%B0%D0%B2%D0%BB%D0%B5%D0%BD%D0%B8%D0%B5_%D1%8D%D0%BA%D1%81%D0%BF%D1%80%D0%B5%D1%81%D1%81%D0%B8%D0%B8_%D0%B3%D0%B5%D0%BD%D0%BE%D0%B2" title="Подавление экспрессии генов – Russian" lang="ru" hreflang="ru" data-title="Подавление экспрессии генов" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target">Русский</a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Gene_silencing" title="Gene silencing – Simple English" lang="en-simple" hreflang="en-simple" data-title="Gene silencing" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target">Simple English</a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%A1%D0%B0%D0%B9%D0%BB%D0%B5%D0%BD%D1%81%D0%B8%D0%BD%D0%B3_%D0%B3%D0%B5%D0%BD%D1%96%D0%B2" title="Сайленсинг генів – Ukrainian" lang="uk" hreflang="uk" data-title="Сайленсинг генів" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target">Українська</a></li><li class="interlanguage-link interwiki-ur mw-list-item"><a href="https://ur.wikipedia.org/wiki/%D8%B3%DA%A9%D9%88%D8%AA_%D9%88%D8%B1%D8%A7%D8%AB%DB%81" title="سکوت وراثہ – Urdu" lang="ur" hreflang="ur" data-title="سکوت وراثہ" data-language-autonym="اردو" data-language-local-name="Urdu" class="interlanguage-link-target">اردو</a></li><li class="interlanguage-link interwiki-zh mw-list-item"><a href="https://zh.wikipedia.org/wiki/%E5%9F%BA%E5%9B%A0%E9%9D%9C%E9%BB%98" title="基因靜默 – Chinese" lang="zh" hreflang="zh" data-title="基因靜默" data-language-autonym="中文" data-language-local-name="Chinese" class="interlanguage-link-target">中文</a></li></ul> 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