Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina
Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of diffe...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-04, Vol.8 (4), p.e60361-e60361 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e60361 |
|---|---|
| container_issue | 4 |
| container_start_page | e60361 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Charbel Issa, Peter De Silva, Samantha R Lipinski, Daniel M Singh, Mandeep S Mouravlev, Alexandre You, Qisheng Barnard, Alun R Hankins, Mark W During, Matthew J Maclaren, Robert E |
| description | Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments. |
| doi_str_mv | 10.1371/journal.pone.0060361 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1330894743</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478361120</galeid><doaj_id>oai_doaj_org_article_1820a8974b324f3c9c2b0755bcd81184</doaj_id><sourcerecordid>A478361120</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-737c529a3cafb13bf4f5330c4d6c37a6c4381163357fd60583370c0431b0c7af3</originalsourceid><addsrcrecordid>eNqNk02L2zAQhk1p6W7T_oPSGgqlPSSVPPLXpRCWfgQWFvqxVyHLo0TBlrKSsm1O_etVEu8Slz0UH2Q0z_tqNJpJkpeUzCiU9MPabp0R3WxjDc4IKQgU9FFyTmvIpkVG4PHJ_1nyzPs1ITlURfE0OcsgjyFCz5M_c-_R-x5NSK1Kg7Mb7ftUmDZFpVAGfYsmAvugwV_pxuleBJy26GKkTVe7xuk2dSht32gjos18fp16dDbsNuhTbdKwwrS3W48H28EhSkLknydPlOg8vhjWSfLz86cfF1-nl1dfFhfzy6ks6ixMSyhlntUCpFANhUYxlQMQydpCQikKyaCitADIS9UWJK8ASiIJA9oQWQoFk-T10XfTWc-H2nlOo0lVs5JBJBZHorVizQ9Zuh23QvPDhnVLLlzQskNOq4yIqi5ZAxlTIGuZNaTM80a2MYuKRa-Pw2nbpsdWxuo60Y1MxxGjV3xpbzkUGa3qPBq8GwycvdmiD7zXXmLXCYOxkjHvrMoZMFJE9M0_6MO3G6iliBfQRtl4rtyb8jkrq9g7NPbJJJk9QMWvxV7L2GhKx_2R4P1IEJmAv8NSbL3ni-_f_p-9uh6zb0_YFYourLzttkFb48cgO4LSWe8dqvsiU8L3c3JXDb6fEz7MSZS9On2ge9HdYMBfPIMNVQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1330894743</pqid></control><display><type>article</type><title>Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Charbel Issa, Peter ; De Silva, Samantha R ; Lipinski, Daniel M ; Singh, Mandeep S ; Mouravlev, Alexandre ; You, Qisheng ; Barnard, Alun R ; Hankins, Mark W ; During, Matthew J ; Maclaren, Robert E</creator><creatorcontrib>Charbel Issa, Peter ; De Silva, Samantha R ; Lipinski, Daniel M ; Singh, Mandeep S ; Mouravlev, Alexandre ; You, Qisheng ; Barnard, Alun R ; Hankins, Mark W ; During, Matthew J ; Maclaren, Robert E</creatorcontrib><description>Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0060361</identifier><identifier>PMID: 23593201</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animal tissues ; Animals ; Biology ; Biomedical research ; Brain ; Cell Line ; Clinical trials ; Degeneration ; Dependovirus - classification ; Dependovirus - physiology ; Drug dosages ; Efficiency ; Gene Expression ; Gene sequencing ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Hospitals ; Humans ; Immune response ; Immune response (cell-mediated) ; Laboratories ; Lymphocytes T ; Medical research ; Medicine ; Mice ; Mice, Transgenic ; Mutation ; Neurodegeneration ; Neurosciences ; Photoreceptors ; Primates ; Proteins ; Recombination, Genetic ; Retina ; Retina - metabolism ; Retina - virology ; Retinal degeneration ; Retinal Degeneration - genetics ; Retinal Degeneration - metabolism ; Rodents ; Serotypes ; Therapeutic applications ; Transduction, Genetic ; Tropism ; Vectors (Biology) ; Viral Tropism</subject><ispartof>PloS one, 2013-04, Vol.8 (4), p.e60361-e60361</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Charbel Issa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Charbel Issa et al 2013 Charbel Issa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-737c529a3cafb13bf4f5330c4d6c37a6c4381163357fd60583370c0431b0c7af3</citedby><cites>FETCH-LOGICAL-c692t-737c529a3cafb13bf4f5330c4d6c37a6c4381163357fd60583370c0431b0c7af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621895/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621895/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23593201$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Charbel Issa, Peter</creatorcontrib><creatorcontrib>De Silva, Samantha R</creatorcontrib><creatorcontrib>Lipinski, Daniel M</creatorcontrib><creatorcontrib>Singh, Mandeep S</creatorcontrib><creatorcontrib>Mouravlev, Alexandre</creatorcontrib><creatorcontrib>You, Qisheng</creatorcontrib><creatorcontrib>Barnard, Alun R</creatorcontrib><creatorcontrib>Hankins, Mark W</creatorcontrib><creatorcontrib>During, Matthew J</creatorcontrib><creatorcontrib>Maclaren, Robert E</creatorcontrib><title>Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.</description><subject>Animal models</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Biology</subject><subject>Biomedical research</subject><subject>Brain</subject><subject>Cell Line</subject><subject>Clinical trials</subject><subject>Degeneration</subject><subject>Dependovirus - classification</subject><subject>Dependovirus - physiology</subject><subject>Drug dosages</subject><subject>Efficiency</subject><subject>Gene Expression</subject><subject>Gene sequencing</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune response (cell-mediated)</subject><subject>Laboratories</subject><subject>Lymphocytes T</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Mutation</subject><subject>Neurodegeneration</subject><subject>Neurosciences</subject><subject>Photoreceptors</subject><subject>Primates</subject><subject>Proteins</subject><subject>Recombination, Genetic</subject><subject>Retina</subject><subject>Retina - metabolism</subject><subject>Retina - virology</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - genetics</subject><subject>Retinal Degeneration - metabolism</subject><subject>Rodents</subject><subject>Serotypes</subject><subject>Therapeutic applications</subject><subject>Transduction, Genetic</subject><subject>Tropism</subject><subject>Vectors (Biology)</subject><subject>Viral Tropism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk02L2zAQhk1p6W7T_oPSGgqlPSSVPPLXpRCWfgQWFvqxVyHLo0TBlrKSsm1O_etVEu8Slz0UH2Q0z_tqNJpJkpeUzCiU9MPabp0R3WxjDc4IKQgU9FFyTmvIpkVG4PHJ_1nyzPs1ITlURfE0OcsgjyFCz5M_c-_R-x5NSK1Kg7Mb7ftUmDZFpVAGfYsmAvugwV_pxuleBJy26GKkTVe7xuk2dSht32gjos18fp16dDbsNuhTbdKwwrS3W48H28EhSkLknydPlOg8vhjWSfLz86cfF1-nl1dfFhfzy6ks6ixMSyhlntUCpFANhUYxlQMQydpCQikKyaCitADIS9UWJK8ASiIJA9oQWQoFk-T10XfTWc-H2nlOo0lVs5JBJBZHorVizQ9Zuh23QvPDhnVLLlzQskNOq4yIqi5ZAxlTIGuZNaTM80a2MYuKRa-Pw2nbpsdWxuo60Y1MxxGjV3xpbzkUGa3qPBq8GwycvdmiD7zXXmLXCYOxkjHvrMoZMFJE9M0_6MO3G6iliBfQRtl4rtyb8jkrq9g7NPbJJJk9QMWvxV7L2GhKx_2R4P1IEJmAv8NSbL3ni-_f_p-9uh6zb0_YFYourLzttkFb48cgO4LSWe8dqvsiU8L3c3JXDb6fEz7MSZS9On2ge9HdYMBfPIMNVQ</recordid><startdate>20130409</startdate><enddate>20130409</enddate><creator>Charbel Issa, Peter</creator><creator>De Silva, Samantha R</creator><creator>Lipinski, Daniel M</creator><creator>Singh, Mandeep S</creator><creator>Mouravlev, Alexandre</creator><creator>You, Qisheng</creator><creator>Barnard, Alun R</creator><creator>Hankins, Mark W</creator><creator>During, Matthew J</creator><creator>Maclaren, Robert E</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130409</creationdate><title>Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina</title><author>Charbel Issa, Peter ; De Silva, Samantha R ; Lipinski, Daniel M ; Singh, Mandeep S ; Mouravlev, Alexandre ; You, Qisheng ; Barnard, Alun R ; Hankins, Mark W ; During, Matthew J ; Maclaren, Robert E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-737c529a3cafb13bf4f5330c4d6c37a6c4381163357fd60583370c0431b0c7af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal models</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Biology</topic><topic>Biomedical research</topic><topic>Brain</topic><topic>Cell Line</topic><topic>Clinical trials</topic><topic>Degeneration</topic><topic>Dependovirus - classification</topic><topic>Dependovirus - physiology</topic><topic>Drug dosages</topic><topic>Efficiency</topic><topic>Gene Expression</topic><topic>Gene sequencing</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune response (cell-mediated)</topic><topic>Laboratories</topic><topic>Lymphocytes T</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mutation</topic><topic>Neurodegeneration</topic><topic>Neurosciences</topic><topic>Photoreceptors</topic><topic>Primates</topic><topic>Proteins</topic><topic>Recombination, Genetic</topic><topic>Retina</topic><topic>Retina - metabolism</topic><topic>Retina - virology</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - genetics</topic><topic>Retinal Degeneration - metabolism</topic><topic>Rodents</topic><topic>Serotypes</topic><topic>Therapeutic applications</topic><topic>Transduction, Genetic</topic><topic>Tropism</topic><topic>Vectors (Biology)</topic><topic>Viral Tropism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Charbel Issa, Peter</creatorcontrib><creatorcontrib>De Silva, Samantha R</creatorcontrib><creatorcontrib>Lipinski, Daniel M</creatorcontrib><creatorcontrib>Singh, Mandeep S</creatorcontrib><creatorcontrib>Mouravlev, Alexandre</creatorcontrib><creatorcontrib>You, Qisheng</creatorcontrib><creatorcontrib>Barnard, Alun R</creatorcontrib><creatorcontrib>Hankins, Mark W</creatorcontrib><creatorcontrib>During, Matthew J</creatorcontrib><creatorcontrib>Maclaren, Robert E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Charbel Issa, Peter</au><au>De Silva, Samantha R</au><au>Lipinski, Daniel M</au><au>Singh, Mandeep S</au><au>Mouravlev, Alexandre</au><au>You, Qisheng</au><au>Barnard, Alun R</au><au>Hankins, Mark W</au><au>During, Matthew J</au><au>Maclaren, Robert E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-04-09</date><risdate>2013</risdate><volume>8</volume><issue>4</issue><spage>e60361</spage><epage>e60361</epage><pages>e60361-e60361</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23593201</pmid><doi>10.1371/journal.pone.0060361</doi><tpages>e60361</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-04, Vol.8 (4), p.e60361-e60361 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330894743 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal models Animal tissues Animals Biology Biomedical research Brain Cell Line Clinical trials Degeneration Dependovirus - classification Dependovirus - physiology Drug dosages Efficiency Gene Expression Gene sequencing Gene therapy Gene transfer Gene Transfer Techniques Genetic Vectors - administration & dosage Genetic Vectors - genetics Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Hospitals Humans Immune response Immune response (cell-mediated) Laboratories Lymphocytes T Medical research Medicine Mice Mice, Transgenic Mutation Neurodegeneration Neurosciences Photoreceptors Primates Proteins Recombination, Genetic Retina Retina - metabolism Retina - virology Retinal degeneration Retinal Degeneration - genetics Retinal Degeneration - metabolism Rodents Serotypes Therapeutic applications Transduction, Genetic Tropism Vectors (Biology) Viral Tropism |
| title | Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T05%3A51%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Assessment%20of%20tropism%20and%20effectiveness%20of%20new%20primate-derived%20hybrid%20recombinant%20AAV%20serotypes%20in%20the%20mouse%20and%20primate%20retina&rft.jtitle=PloS%20one&rft.au=Charbel%20Issa,%20Peter&rft.date=2013-04-09&rft.volume=8&rft.issue=4&rft.spage=e60361&rft.epage=e60361&rft.pages=e60361-e60361&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0060361&rft_dat=%3Cgale_plos_%3EA478361120%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330894743&rft_id=info:pmid/23593201&rft_galeid=A478361120&rft_doaj_id=oai_doaj_org_article_1820a8974b324f3c9c2b0755bcd81184&rfr_iscdi=true |