EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat
Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based len...
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| Veröffentlicht in: | PloS one 2014-04, Vol.9 (4), p.e94272-e94272 |
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| creator | Zallocchi, Marisa Binley, Katie Lad, Yatish Ellis, Scott Widdowson, Peter Iqball, Sharifah Scripps, Vicky Kelleher, Michelle Loader, Julie Miskin, James Peng, You-Wei Wang, Wei-Min Cheung, Linda Delimont, Duane Mitrophanous, Kyriacos A Cosgrove, Dominic |
| description | Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome. |
| doi_str_mv | 10.1371/journal.pone.0094272 |
| format | Article |
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Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0094272</identifier><identifier>PMID: 24705452</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Blindness ; Care and treatment ; Cell Line ; Congenital diseases ; Deafness ; Degeneration ; Disease Models, Animal ; Expression vectors ; Eye (anatomy) ; FDA approval ; Female ; Gene mutations ; Gene Order ; Gene therapy ; Genetic aspects ; Genetic Therapy ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Genetic Vectors - metabolism ; Humans ; Infectious Anemia Virus, Equine - genetics ; Laboratories ; Light ; Light intensity ; Light levels ; Localization ; Luminous intensity ; Macaca ; Male ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Mutation ; Myosin ; Myosin VIIA ; Myosins - genetics ; Phenotype ; Photoreception ; Photoreceptor Cells - metabolism ; Photoreceptor Cells - pathology ; Photoreceptors ; Physiological aspects ; Protein Transport ; Proteins ; Research and Analysis Methods ; Restoration ; Retina ; Retina - metabolism ; Retina - pathology ; Retinal degeneration ; Safety ; Science ; Stainless steel ; Studies ; Transducin ; Transducin - metabolism ; Translocation ; Usher Syndromes - genetics ; Usher Syndromes - therapy ; Usher's syndrome ; Vectors (Biology)</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e94272-e94272</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Zallocchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://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>2014 Zallocchi et al 2014 Zallocchi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b3c0fc72228f905edff44c21a3ef904f2c684a7226bd3d186b18935de7f48e4d3</citedby><cites>FETCH-LOGICAL-c692t-b3c0fc72228f905edff44c21a3ef904f2c684a7226bd3d186b18935de7f48e4d3</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/PMC3976400/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976400/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24705452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rendon, Alvaro</contributor><creatorcontrib>Zallocchi, Marisa</creatorcontrib><creatorcontrib>Binley, Katie</creatorcontrib><creatorcontrib>Lad, Yatish</creatorcontrib><creatorcontrib>Ellis, Scott</creatorcontrib><creatorcontrib>Widdowson, Peter</creatorcontrib><creatorcontrib>Iqball, Sharifah</creatorcontrib><creatorcontrib>Scripps, Vicky</creatorcontrib><creatorcontrib>Kelleher, Michelle</creatorcontrib><creatorcontrib>Loader, Julie</creatorcontrib><creatorcontrib>Miskin, James</creatorcontrib><creatorcontrib>Peng, You-Wei</creatorcontrib><creatorcontrib>Wang, Wei-Min</creatorcontrib><creatorcontrib>Cheung, Linda</creatorcontrib><creatorcontrib>Delimont, Duane</creatorcontrib><creatorcontrib>Mitrophanous, Kyriacos A</creatorcontrib><creatorcontrib>Cosgrove, Dominic</creatorcontrib><title>EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.</description><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Blindness</subject><subject>Care and treatment</subject><subject>Cell Line</subject><subject>Congenital diseases</subject><subject>Deafness</subject><subject>Degeneration</subject><subject>Disease Models, Animal</subject><subject>Expression vectors</subject><subject>Eye (anatomy)</subject><subject>FDA approval</subject><subject>Female</subject><subject>Gene mutations</subject><subject>Gene Order</subject><subject>Gene therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - metabolism</subject><subject>Humans</subject><subject>Infectious Anemia Virus, Equine - 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metabolism</subject><subject>Translocation</subject><subject>Usher Syndromes - genetics</subject><subject>Usher Syndromes - therapy</subject><subject>Usher's syndrome</subject><subject>Vectors (Biology)</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11r1EAUhoMotlb_geiAIHqx63wlM_FCWEvVhULB2t4Ok8yZTWqSiTNJcf-9s25aNtILCUzm43nfk3MyJ0leErwkTJAPN270nW6WvetgiXHOqaCPkmOSM7rIKGaPD-ZHybMQbjBOmcyyp8kR5QKnPKXHSXu2Xl0vCh3AIA9DHR3RBjpAQwVe91tUd7spCpX-CZ6g1o0B4migQdZ5NIbIobDtjHdtVG17QOTzR2TgFhrXt9ANyFl0FarLQQ_PkydWNwFeTO-T5OrL2Y_Tb4vzi6_r09X5osxyOiwKVmJbCkqptDlOwVjLeUmJZhDX3NIyk1zH86wwzBCZFUTmLDUgLJfADTtJXu99-8YFNVUqKJILIbhgqYjEek8Yp29U7-tW-61yulZ_N5zfKO2HumxAkZTmuZE2MwTzGFFqKQrAOZUmj5F30T5N0caiBVPGnL1uZqbzk66u1MbdKpaLjGMcDd5NBt79GiEMqq1DCU2jO4j1jl9AOGdM5iSib_5BH85uojY6JlB31sW45c5UrZhIU8m4zCK1fICKj4G2LuO1snXcnwnezwSRGeD3sNFjCGp9-f3_2YvrOfv2gK1AN0MVXDMOtevCHOR7sPQuBA_2vsgEq11X3FVD7bpCTV0RZa8Of9C96K4N2B9MSwbm</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Zallocchi, Marisa</creator><creator>Binley, Katie</creator><creator>Lad, Yatish</creator><creator>Ellis, Scott</creator><creator>Widdowson, Peter</creator><creator>Iqball, Sharifah</creator><creator>Scripps, Vicky</creator><creator>Kelleher, Michelle</creator><creator>Loader, Julie</creator><creator>Miskin, James</creator><creator>Peng, You-Wei</creator><creator>Wang, Wei-Min</creator><creator>Cheung, Linda</creator><creator>Delimont, Duane</creator><creator>Mitrophanous, Kyriacos A</creator><creator>Cosgrove, Dominic</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>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>20140401</creationdate><title>EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat</title><author>Zallocchi, Marisa ; Binley, Katie ; Lad, Yatish ; Ellis, Scott ; Widdowson, Peter ; Iqball, Sharifah ; Scripps, Vicky ; Kelleher, Michelle ; Loader, Julie ; Miskin, James ; Peng, You-Wei ; Wang, Wei-Min ; Cheung, Linda ; Delimont, Duane ; Mitrophanous, Kyriacos A ; Cosgrove, Dominic</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b3c0fc72228f905edff44c21a3ef904f2c684a7226bd3d186b18935de7f48e4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Blindness</topic><topic>Care and treatment</topic><topic>Cell Line</topic><topic>Congenital diseases</topic><topic>Deafness</topic><topic>Degeneration</topic><topic>Disease Models, Animal</topic><topic>Expression vectors</topic><topic>Eye (anatomy)</topic><topic>FDA approval</topic><topic>Female</topic><topic>Gene mutations</topic><topic>Gene Order</topic><topic>Gene therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors - 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metabolism</topic><topic>Translocation</topic><topic>Usher Syndromes - genetics</topic><topic>Usher Syndromes - therapy</topic><topic>Usher's syndrome</topic><topic>Vectors (Biology)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zallocchi, Marisa</creatorcontrib><creatorcontrib>Binley, Katie</creatorcontrib><creatorcontrib>Lad, Yatish</creatorcontrib><creatorcontrib>Ellis, Scott</creatorcontrib><creatorcontrib>Widdowson, Peter</creatorcontrib><creatorcontrib>Iqball, Sharifah</creatorcontrib><creatorcontrib>Scripps, Vicky</creatorcontrib><creatorcontrib>Kelleher, Michelle</creatorcontrib><creatorcontrib>Loader, Julie</creatorcontrib><creatorcontrib>Miskin, James</creatorcontrib><creatorcontrib>Peng, You-Wei</creatorcontrib><creatorcontrib>Wang, Wei-Min</creatorcontrib><creatorcontrib>Cheung, Linda</creatorcontrib><creatorcontrib>Delimont, Duane</creatorcontrib><creatorcontrib>Mitrophanous, Kyriacos A</creatorcontrib><creatorcontrib>Cosgrove, Dominic</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 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 - 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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>Zallocchi, Marisa</au><au>Binley, Katie</au><au>Lad, Yatish</au><au>Ellis, Scott</au><au>Widdowson, Peter</au><au>Iqball, Sharifah</au><au>Scripps, Vicky</au><au>Kelleher, Michelle</au><au>Loader, Julie</au><au>Miskin, James</au><au>Peng, You-Wei</au><au>Wang, Wei-Min</au><au>Cheung, Linda</au><au>Delimont, Duane</au><au>Mitrophanous, Kyriacos A</au><au>Cosgrove, Dominic</au><au>Rendon, Alvaro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>e94272</spage><epage>e94272</epage><pages>e94272-e94272</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24705452</pmid><doi>10.1371/journal.pone.0094272</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-04, Vol.9 (4), p.e94272-e94272 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1977747357 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Biology and Life Sciences Blindness Care and treatment Cell Line Congenital diseases Deafness Degeneration Disease Models, Animal Expression vectors Eye (anatomy) FDA approval Female Gene mutations Gene Order Gene therapy Genetic aspects Genetic Therapy Genetic Vectors - administration & dosage Genetic Vectors - genetics Genetic Vectors - metabolism Humans Infectious Anemia Virus, Equine - genetics Laboratories Light Light intensity Light levels Localization Luminous intensity Macaca Male Medicine and Health Sciences Mice Mice, Knockout Mutation Myosin Myosin VIIA Myosins - genetics Phenotype Photoreception Photoreceptor Cells - metabolism Photoreceptor Cells - pathology Photoreceptors Physiological aspects Protein Transport Proteins Research and Analysis Methods Restoration Retina Retina - metabolism Retina - pathology Retinal degeneration Safety Science Stainless steel Studies Transducin Transducin - metabolism Translocation Usher Syndromes - genetics Usher Syndromes - therapy Usher's syndrome Vectors (Biology) |
| title | EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat |
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