Gene Therapy Retrovirus Vectors Explained

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All The genetic material in <a href="/glossary-of-gene-therapy-terms.html#retrovirus">retroviruses</a> is in the form of <a href="/glossary-of-gene-therapy-terms.html#rna">RNA</a> molecules, while the genetic material of their hosts is in the form of <a href="/glossary-of-gene-therapy-terms.html#dna">DNA</a>. When a retrovirus infects a host cell, it will introduce its RNA together with some <a href="/glossary-of-gene-therapy-terms.html#enzyme">enzymes</a> into the cell. This RNA molecule from the retrovirus must produce a DNA copy from its RNA molecule before it can be considered part of the genetic material of the host cell. Retrovirus genomes commonly contain these three open reading frames that encode for proteins that can be found in the mature virus. Group-specific antigen (gag) codes for core and structural proteins of the virus, polymerase (pol) codes for reverse transcriptase, protease and integrase, and envelope (env) codes for the retroviral coat proteins (see figure 1).<br /> <img border="0" src="/images/retrovirusgenome.JPG" /><br /> <em>Figure 1. Genome organisation of retroviruses.</em><br /><br /><center><br /> <div class="moduletable "> <div class="mod-banners bannergroup"> <div class="mod-banners__item banneritem"> <a href="/component/banners/click/160.html" target="_blank" rel="noopener noreferrer" title="8thAntigen-SpecImmunTol-feb2025"> <img src="https://www.genetherapynet.com/images/banners/8thAntigen-SpecImmunTol-feb2025.jpg#joomlaImage://local-images/banners/8thAntigen-SpecImmunTol-feb2025.jpg?width=468&height=60" alt="8thAntigen-SpecImmunTol-feb2025" > </a> </div> </div> </div> </center> <p>The process of producing a DNA copy from an RNA molecule is termed reverse <a href="/glossary-of-gene-therapy-terms.html#transcription">transcription</a>. It is carried out by one of the enzymes carried in the virus, called reverse transcriptase. After this DNA copy is produced and is free in the <a href="/glossary-of-gene-therapy-terms.html#nucleus">nucleus</a> of the host cell, it must be incorporated into the <a href="/glossary-of-gene-therapy-terms.html#genome">genome</a> of the host cell. That is, it must be inserted into the large DNA molecules in the cell (the <a href="/glossary-of-gene-therapy-terms.html#chromosomes">chromosomes</a>). This process is done by another enzyme carried in the virus called integrase (see figure 2).</p> <p>Now that the genetic material of the virus is incorporated and has become part of the genetic material of the host cell, we can say that the host cell is now <a href="/glossary-of-gene-therapy-terms.html#geneticengineering">modified</a> to contain a new gene. If this host cell divides later, its descendants will all contain the new genes. Sometimes the <a href="/glossary-of-gene-therapy-terms.html#gene">genes</a> of the retrovirus do not <a href="/glossary-of-gene-therapy-terms.html#geneexpression">express</a> their information immediately.</p> <img border="0" src="/images/retrovirusintegration.JPG" /><br /> <em>Figure 2. Integration of retroviruses</em>.<br /> <p>Retroviral vectors are created by removal op the retroviral gag, pol, and env genes. These are replaced by the therapeutic gene. In order to produce vector particles a packaging cell is essential. Packaging cell lines provide all the viral proteins required for capsid production and the virion maturation of the vector. These packaging cell lines have been made so that they contain the gag, pol and env genes. Early packaging cell lines contained replication competent retroviral genomes and a single recombination event between this genome and the retroviral DNA vector could result in the production of a wild type virus. Following insertion of the desired gene into in the retroviral DNA vector, and maintainance of the proper packaging cell line, it is now a simple matter to prepare retroviral vectors (see figure 3).</p> <img border="0" src="/images/retroviralvector.JPG" width="393" height="549" /><br /> <em>Figure 3. Producing recombinant retroviral vectors</em>.<br /> <p>One of the problems of <a href="/glossary-of-gene-therapy-terms.html#genetherapy">gene therapy</a> using retroviruses is that the integrase enzyme can insert the genetic material of the virus in any arbitrary position in the genome of the host. If genetic material happens to be inserted in the middle of one of the original genes of the host cell, this gene will be disrupted (insertional <a href="/glossary-of-gene-therapy-terms.html#mutation">mutagenesis</a>). If the gene happens to be one regulating cell division, uncontrolled cell division (i.e., cancer) can occur. This problem has recently begun to be addressed by utilizing zinc finger nucleases or by including certain sequences such as the beta-globin locus control region to direct the site of integration to specific chromosomal sites.</p> <p><a href="/glossary-of-gene-therapy-terms.html#clinicaltrial">Gene therapy trials</a> to treat <a href="/glossary-of-gene-therapy-terms.html#immunodeficiency">severe combined immunodeficiency (SCID)</a> were halted or restricted in the USA when <a href="/glossary-of-gene-therapy-terms.html#leukemia">leukemia</a> was reported in three of eleven patients treated in the French X-linked SCID (<a href="/glossary-of-gene-therapy-terms.html#x-scid">X-SCID</a>) gene therapy trial. Ten X-SCID patients treated in England have not presented leukemia to date and have had similar success in immune reconstitution. Gene therapy trials to treat SCID due to deficiency of the Adenosine Deaminase (<a href="/glossary-of-gene-therapy-terms.html#ada">ADA</a>) enzyme continue with relative success in the USA, Italy and Japan.</p> <p>As a reaction to the adverse events in the French X-SCID gene therapy trial, the Recombinant DNA Advisory Committee sent a letter to Principal Investigators Conveying RAC Recommendations in 2003. In addition, the RAC published conclusions and recommendations of the RAC Gene Transfer Safety Symposium in 2005. A joint working party of the Gene Therapy Advisory Committee and the Committee on Safety of Medicines (CSM) in the UK lead to the publication of an updated recommendations of the GTAC/CSM working party on retroviruses in 2005.</p> <center> <style> .aangepast { width: 320px; } @media(min-width: 500px) { .aangepast { width: 468px; } ) @media(min-width: 800px) { .aangepast { width: 468px; } } </style> <script async src="https://pagead2.googlesyndication.com/pagead/js/adsbygoogle.js"></script> <ins class="adsbygoogle aangepast" style="display:block; text-align:center;" data-ad-layout="in-article" data-ad-format="fluid" data-ad-client="ca-pub-1253043591735915" data-ad-slot="5059787231"></ins> <script> (adsbygoogle = window.adsbygoogle || []).push({}); </script> </center> <br /> <div align="right"><a href="#top"><span style="font-size: xx-small;" size="1">^ Back to Top</span></a></div></div> <div class="uk-margin-top"><a href="/viral-vector/retroviruses.html" class="el-link uk-button uk-button-default">Read more</a></div> </div></div> </div> </div> </div> <div class="uk-width-1-2 uk-width-1-4@m uk-width-1-5@l rechts"> <div> <div class="uk-grid uk-child-width-1-1 uk-grid-row-small" uk-grid> <div> <div class="uk-panel _menu menulist" id="module-32"> <h3> What is Gene Therapy </h3> <ul class="uk-nav uk-nav-default"> <li class="item-26"><a href="/basic-process.html"> Basic Process</a></li> <li class="item-27"><a href="/types-of-gene-therapy.html"> Types of gene therapy</a></li> <li class="item-28"><a href="/gene-doping.html"> Gene Doping</a></li> <li class="item-29 uk-active uk-parent"><a href="/viral-vectors.html"> Viral Vectors</a> <ul class="uk-nav-sub"> <li class="item-30"><a href="/viral-vector/adenoviruses.html"> Adenoviruses</a></li> <li class="item-31"><a href="/viral-vector/adeno-associated-viruses.html"> Adeno-associated viruses</a></li> <li class="item-32"><a href="/viral-vector/alphaviruses.html"> Alphaviruses</a></li> <li class="item-33"><a href="/viral-vector/herpesviruses.html"> Herpesviruses</a></li> <li class="item-34"><a href="/viral-vector/lentiviruses.html"> Lentiviruses</a></li> <li class="item-35 uk-active"><a href="/viral-vector/retroviruses.html"> Retroviruses</a></li> <li class="item-36"><a href="/viral-vector/vaccinia-viruses.html"> Vaccinia viruses</a></li> <li class="item-132"><a href="/viral-vector/risk-factors.html"> Risk Factors</a></li> <li class="item-133"><a href="/viral-vector/pseudotyping-of-viral-vectors.html"> Pseudotyping of Viral Vectors</a></li></ul></li> <li class="item-37 uk-parent"><a href="/non-viral-vectors.html"> Non-viral Vectors</a> <ul class="uk-nav-sub"> <li class="item-129"><a href="/non-viral-vectors/naked-dna.html"> Naked DNA</a></li> <li class="item-130"><a href="/non-viral-vectors/oligonucleotides.html"> Oligonucleotides</a></li> <li class="item-131"><a href="/non-viral-vectors/lipoplexes-and-polyplexes.html"> Lipoplexes and polyplexes</a></li></ul></li> <li class="item-709 uk-parent"><a href="/gene-editing-tools.html"> Gene Editing Tools</a> <ul class="uk-nav-sub"> <li class="item-710"><a href="/gene-editing-tools/zinc-finger-nuclease.html"> Zinc Finger Nuclease</a></li> <li class="item-711"><a href="/gene-editing-tools/talen.html"> TALEN</a></li> <li class="item-712"><a href="/gene-editing-tools/crispr-cas9.html"> CRISPR-Cas9 </a></li></ul></li> <li class="item-38"><a href="/glossary-of-gene-therapy-terms.html"> Glossary of Gene Therapy Terms</a></li></ul> </div> </div> <div> <div class="uk-panel" id="module-40"> <h3> Resources </h3> <div class="uk-margin-remove-last-child custom" ><ul class="resources"> <li><a href="https://www.acgtfoundation.org" target="_blank">Alliance for Cancer Gene Therapy</a></li> <li><a href="https://www.cancer.org" target="_blank">American Cancer Society</a></li> <li><a href="https://www.bio-medicine.org" target="_blank">Bio-Medicine</a></li> <li><a href="https://www.bioscience-explained.org" target="_blank">Bioscience Explained</a></li> <li><a href="https://kidshealth.org/parent/system/medical/gene_therapy.html" target="_blank">Gene Therapy and Children, KidsHealth</a></li><li><a href="https://learn.genetics.utah.edu/content/genetherapy/" target="_blank">Genetic Science Learning Center</a></li> <li><a href="https://www.ornl.gov/sci/techresources/Human_Genome/home.shtml" target="_blank">Human Genome Project Information</a></li> <li><a href="https://ictvonline.org/" target="_blank">ICTVdB, The Universal Virus Database</a></li> <li><a href="https://www.iupui.edu/~wellsctr/MMIA/htm/animations.htm" target="_blank">Molecular Medicine in Action</a></li> <li><a href="https://www.cancer.gov" target="_blank">National Cancer Institute</a></li> <li><a href="https://www.genome.gov/Education/" target="_blank">Understanding the Human Genome Project - Online education kit</a></li> <li><a href="https://www.virology.net/garryfavwebgenether.html" target="_blank">Viral Vectors and Gene Therapy, All the Virology on the www</a></li> <li><a href="https://en.wikipedia.org/wiki/Wikipedia" target="_blank">Wikipedia</a></li> <hr /> <li> <a href="https://images.google.com/images?hl=en&q=%22gene+therapy'&um=1&ie=UTF-8&sa=N&tab=wi" target="_blank">Images of gene therapy</a></li> <li><a href="https://www.google.com/search?hl=nl&q=%22gene+therapy%22+.ppt&meta=" target="_blank">PowerPoint presentations on gene therapy</a></li> <li><a href="https://nl.youtube.com/results?search_query=+%22gene+therapy%22&as=1&and_queries=&exact_query=gene+therapy&or_queries=&negative_queries=&geo_name=&geo_latlong=&search_duration=&search_hl=&search_category_type=specific&search_category=28&search_sort=&uploaded=" target="_blank">YouTube videos about gene therapy</a></li> </ul> <div align="center"> <form action="https://www.wikipedia.org/search-redirect.php" method="get" target="_blank"> <table> <tr><td nowrap="nowrap" valign="top" align="center" height="32"><img src="/images/wikipedia.gif" alt="Search Wikipedia" width="75" height="84" border="0" /> <input type="hidden" name="language" value="en"> </td></tr> <tr><td valign="top" align="center"> <input type="text" name="search" size="18" value="Wikipedia search..." style="background:#ffffff; color:#666666" onfocus="if(this.value=='Wikipedia search...'){this.value='';}" onblur="if(this.value==''){this.value='Wikipedia search...';}"> </td></tr> <tr><td valign="top" align="center"> <input type="submit" name="go" value="Search"> </td></tr></table> </form> </div></div> </div> </div> <div> <div class="uk-panel" id="module-130"> <h3> Retrovirus Books </h3> <div class="uk-margin-remove-last-child custom" ><div align="center"> <iframe src="https://rcm-na.amazon-adsystem.com/e/cm?t=genthenet-20&o=1&p=8&l=as1&asins=1904455557&fc1=000000&IS2=1&lt1=_blank&lc1=000000&bc1=E3E5E6&bg1=E3E5E6&f=ifr" style="width:120px;height:240px;" scrolling="no" marginwidth="0" marginheight="0" frameborder="0"></iframe> <br /> <iframe 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