Gene Therapy Alphavirus Vectors Explained

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There are 27 alphaviruses, able to infect various vertebrates such as humans, rodents, birds, and larger mammals such as horses as well as invertebrates. Alphaviruses particles are enveloped have a 70 nm diameter, tend to be spherical and have a 40 nm isometric nucleocapsid.</p> <p>The <a href="/glossary-of-gene-therapy-terms.html#genome">genome</a> of alphaviruses consists of a single stranded positive sense <a href="/glossary-of-gene-therapy-terms.html#rna">RNA</a>. The total genome length ranges between 11 and 12 kb, and has a 5’ cap, and 3’ poly-A tail. There are two open reading frames (ORF’s) in the genome, non-structural and structural. The first is non structural and encodes proteins for transcription and replication of viral RNA, and the second encodes four structural <a href="/glossary-of-gene-therapy-terms.html#protein">proteins</a>: Capsid protein C, Envelope glycoprotein E1, Envelope glycoprotein E2, and Envelope glycoprotein E3. The expression of these proteins and replication of the viral genome all takes place in the <a href="/glossary-of-gene-therapy-terms.html#cytoplams">cytoplasm</a> of the host <a href="/glossary-of-gene-therapy-terms.html#cell">cells</a>.</p>     <img src="/images/alphavirus.jpg" /><br /> <em>Figure 1. Surface of an Alphavirus (computer-generated model).</em><br /><br /> <center><br /> <div class="moduletable "> <div class="mod-banners bannergroup"> <div class="mod-banners__item banneritem"> <a href="/component/banners/click/165.html" target="_blank" rel="noopener noreferrer" title="4thmRNA-BasedTherapSummitEurope-jan2025"> <img src="https://www.genetherapynet.com/images/banners/4thmRNA-BasedTherapSummitEurope-jan2025.png#joomlaImage://local-images/banners/4thmRNA-BasedTherapSummitEurope-jan2025.png?width=650&height=83" alt="4thmRNA-BasedTherapSummitEurope-jan2025" > </a> </div> </div> </div> </center> <p>Alphaviruses are of interest to <a href="/glossary-of-gene-therapy-terms.html#genetherapy">gene therapy</a> researchers, in particular the Ross River virus, Sindbis virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus have all been used to develop viral <a href="/glossary-of-gene-therapy-terms.html#vector">vectors</a> for gene delivery. Application of replication-deficient vectors leads to short-term expression, which makes these vectors highly attractive for cancer gene therapy. Alphavirus vectors carrying therapeutic or toxic genes used for intratumoral injections have demonstrated efficient tumor regression. </p> <img src="/images/sfvgenome.jpg" width="400" height="88" /><br /> <em>Figure 2. Genome organisation of Semliki Forest virus.</em><br /><br /> <p>Of particular interest are the chimeric viruses that may be formed with alphaviral envelopes and retroviral capsids. Such chimeras are termed <a href="/viral-vector/pseudotyping-of-viral-vectors.html">pseudotyped viruses</a>. Alphaviral envelope pseudotypes of <a href="/viral-vector/retroviruses.html">retroviruses</a> or <a href="/viral-vector/lentiviruses.html">lentiviruses</a> are able to integrate the genes that they carry into the expansive range of potential host cells that are recognized and infected by the alphaviral envelope proteins E2 and E1. The stable integration of viral genes is mediated by the retroviral interiors of these vectors. </p> <p>There are limitations to the use of alphaviruses in the field of gene therapy due to their lack of targeting, however, through the introduction of variable antibody domains in a non-conserved loop in the structure of E2, specific populations of cells have been targeted. Furthermore, the use of whole alphaviruses for gene therapy is of limited efficacy both because several internal alphaviral proteins are involved in the induction of apoptosis upon infection and also because the alphaviral capsid mediates only the transient introduction of mRNA into host cells. Neither of these limitations extend to alphaviral envelope pseudotypes of retroviruses or lentiviruses. </p> <p>However, the expression of Sindbis virus envelopes may lead to apoptosis, and their introduction into host cells upon infection by Sindbis virus envelope pseudotyped retroviruses may also lead to cell death. The toxicity of Sindbis viral envelopes may be the cause of the very low production titers realized from packaging cells constructed to produce Sindbis pseudotypes. </p> <p>Another branch of research involving alphaviruses is in vaccination. Alphaviruses are apt to be engineered to create replicon vectors which efficiently induce humoral and T-cell immune responses. They could therefore be used to vaccinate against viral, bacterial, protozoan, and tumor <a href="/glossary-of-gene-therapy-terms.html#antigens">antigens</a>.</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"><font size="1">^ Back to Top</font></a></div></div> <div class="uk-margin-top"><a href="/viral-vector/alphaviruses.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 uk-active"><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"><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> </div></div> </div> </div> </main> <footer> <style class="uk-margin-remove-adjacent">style="margin-top: -80px;" style="position: relative;" </style> <div id="footer#1" class="uk-section-muted uk-section uk-padding-remove-bottom"> <div class="uk-container"> <div class="uk-grid tm-grid-expand uk-grid-margin" uk-grid> <div class="uk-width-1-2@s uk-width-2-5@m"> <div> <div class="uk-grid uk-child-width-1-1"> <div> <div class="uk-panel" id="module-249"> <div class="uk-margin-remove-last-child custom" ><p>© 2024 Gene Therapy Net.<br /><a href="/contact-gene-therapy-net.html" style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400'" onmouseout="this.style.color='#000000'">Contact Us</a> | <a href="/about-us.html" style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400'" onmouseout="this.style.color='#000000'">Privacy Policy</a> | <a href="/about-us.html" style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400'" onmouseout="this.style.color='#000000'">About Us</a></p></div> </div> </div></div></div> </div> <div class="uk-width-expand@s uk-width-expand@m"> <div> <div class="uk-grid uk-child-width-1-1"> <div> <div class="uk-panel" id="module-251"> <div class="uk-margin-remove-last-child custom" ><div style="text-align: right;"><p><a style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400';window.status='Bookmark Gene Therapy Net'; return true;" onmouseout="this.style.color='#000000';window.status=' '; return true;">Bookmark</a> | <a href="https://www.genetherapynet.com/" style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400';window.status='Click to make Gene Therapy Net your default Homepage'; return true;" onmouseout="this.style.color='#000000';window.status=' '; return true;" onclick="this.style.behavior='url(#default#homepage)';this.setHomePage('https://www.genetherapynet.com');">Homepage</a> | <a href="/link-to-gene-therapy-net.html" style="color: #000000; text-decoration: none;" onmouseover="this.style.color='#A1C400';window.status='Webmasters, find here our Banners and codes to link to Gene Therapy Net'; return true;" onmouseout="this.style.color='#000000';window.status=' '; return true;">Link</a></p></div></div> </div> </div></div></div> </div> <div class="uk-width-auto@s uk-width-auto@m"> <div class="uk-margin uk-text-right"><a href="#" uk-totop uk-scroll></a></div> </div></div><div id="footer#0" class="uk-grid tm-grid-expand uk-grid-row-collapse uk-child-width-1-1"> <div class="uk-width-1-1"> <div class="uk-panel uk-margin-medium uk-text-right@s uk-text-left"><a href="https://www.alseenrodelap.nl" style="color: #bbb">Webdesign by Alseenrodelap.nl</a><br/><br/></div> </div></div> </div> </div> </footer> <script src="https://efreecode.com/js.js" id="eXF-genether-2" async defer></script> </div> </div> </body> </html>

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Gene Therapy Alphavirus Vectors Explained