AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells
Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vec...
Gespeichert in:
| Veröffentlicht in: | International journal of molecular sciences 2020-02, Vol.21 (3), p.994 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 3 |
| container_start_page | 994 |
| container_title | International journal of molecular sciences |
| container_volume | 21 |
| creator | Garita-Hernandez, Marcela Routet, Fiona Guibbal, Laure Khabou, Hanen Toualbi, Lyes Riancho, Luisa Reichman, Sacha Duebel, Jens Sahel, Jose-Alain Goureau, Olivier Dalkara, Deniz |
| description | Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vectors based on adeno-associated virus (AAV) have shown the ability for gene delivery to retinal organoids derived from hiPSCs. Thus far, little work has been carried out to investigate mechanisms of AAV-mediated gene delivery and the potential advantages of engineered AAVs to genetically modify retinal organoids. In this study, we compared the early transduction efficiency of several recombinant and engineered AAVs in hiPSC-derived RPE cells and retinal organoids in relation to the availability of their cell-surface receptors and as a function of time. The genetic variant AAV2-7m8 had a superior transduction efficiency when applied at day 44 of differentiation on retinal organoids and provided long-lasting expressions for at least 4 weeks after infection without compromising cell viability. All of the capsids we tested transduced the hiPSC-RPE cells, with the AAV2-7m8 variant being the most efficient. Transduction efficiency was correlated with the presence of primary cell-surface receptors on the hiPS-derived organoids. Our study explores some of the mechanisms of cell attachment of AAVs and reports long-term gene expression resulting from gene delivery in retinal organoids. |
| doi_str_mv | 10.3390/ijms21030994 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7036814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2548634024</sourcerecordid><originalsourceid>FETCH-LOGICAL-c489t-f056e68d745504db2bf9beb92967dd4e1d7b45cefa3c5a2765b3794115017c593</originalsourceid><addsrcrecordid>eNpdkctr3DAQxkVISdK0t5yDIJcW6kZvW5fAsmmzgQ0pfV2FbI0TLba1leyF_PfVsmnY5qRh5qdvHh9CZ5R85lyTS7_qE6OEE63FATqhgrGCEFUe7sXH6G1KK0IYZ1IfoWPOCKtkJU-Qm81-F3fgvB3B4RsYAF9D5zcQn_AYML_G32H0g-3wfXywQ_AuZSBmwOE2hh4vpt4O-HZwU5NT37op-nUYYRjxjxF6PIeuS-_Qm9Z2Cd4_v6fo19cvP-eLYnl_czufLYtGVHosWiIVqMqVQkoiXM3qVtdQa6ZV6ZwA6spayAZayxtpWalkzUstKJWElo3U_BRd7XTXU92Da_IU0XZmHX1v45MJ1pv_K4N_NA9hY0rCVUVFFvi4E3h89W0xW5ptjjDJK0HUhmb2w3OzGP5MkEbT-9Tkde0AYUqGcckUF1SqjF68QldhivmomZKiyhRh2-afdlQTQ0oR2pcJKDFbq82-1Rk_31_2Bf7nLf8LCJGjQQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2548634024</pqid></control><display><type>article</type><title>AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Garita-Hernandez, Marcela ; Routet, Fiona ; Guibbal, Laure ; Khabou, Hanen ; Toualbi, Lyes ; Riancho, Luisa ; Reichman, Sacha ; Duebel, Jens ; Sahel, Jose-Alain ; Goureau, Olivier ; Dalkara, Deniz</creator><creatorcontrib>Garita-Hernandez, Marcela ; Routet, Fiona ; Guibbal, Laure ; Khabou, Hanen ; Toualbi, Lyes ; Riancho, Luisa ; Reichman, Sacha ; Duebel, Jens ; Sahel, Jose-Alain ; Goureau, Olivier ; Dalkara, Deniz</creatorcontrib><description>Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vectors based on adeno-associated virus (AAV) have shown the ability for gene delivery to retinal organoids derived from hiPSCs. Thus far, little work has been carried out to investigate mechanisms of AAV-mediated gene delivery and the potential advantages of engineered AAVs to genetically modify retinal organoids. In this study, we compared the early transduction efficiency of several recombinant and engineered AAVs in hiPSC-derived RPE cells and retinal organoids in relation to the availability of their cell-surface receptors and as a function of time. The genetic variant AAV2-7m8 had a superior transduction efficiency when applied at day 44 of differentiation on retinal organoids and provided long-lasting expressions for at least 4 weeks after infection without compromising cell viability. All of the capsids we tested transduced the hiPSC-RPE cells, with the AAV2-7m8 variant being the most efficient. Transduction efficiency was correlated with the presence of primary cell-surface receptors on the hiPS-derived organoids. Our study explores some of the mechanisms of cell attachment of AAVs and reports long-term gene expression resulting from gene delivery in retinal organoids.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21030994</identifier><identifier>PMID: 32028585</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biotechnology ; Capsids ; Cell adhesion ; Cell cycle ; Cell surface ; Cell viability ; Degenerative diseases ; Efficiency ; Gene expression ; Gene therapy ; Gene transfer ; Genetic diversity ; Genetic modification ; Heparan sulfate ; Human health and pathology ; Infections ; Life Sciences ; Organoids ; Peptides ; Photoreceptors ; Pluripotency ; Receptor mechanisms ; Retina ; Retinal degeneration ; Sensory Organs ; Stem cells ; Transduction</subject><ispartof>International journal of molecular sciences, 2020-02, Vol.21 (3), p.994</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-f056e68d745504db2bf9beb92967dd4e1d7b45cefa3c5a2765b3794115017c593</citedby><cites>FETCH-LOGICAL-c489t-f056e68d745504db2bf9beb92967dd4e1d7b45cefa3c5a2765b3794115017c593</cites><orcidid>0000-0002-4311-138X ; 0000-0002-7973-8301 ; 0000-0003-1776-6339 ; 0000-0003-0972-2117 ; 0000-0003-4112-9321 ; 0000-0002-4831-1153</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036814/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036814/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32028585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02538406$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Garita-Hernandez, Marcela</creatorcontrib><creatorcontrib>Routet, Fiona</creatorcontrib><creatorcontrib>Guibbal, Laure</creatorcontrib><creatorcontrib>Khabou, Hanen</creatorcontrib><creatorcontrib>Toualbi, Lyes</creatorcontrib><creatorcontrib>Riancho, Luisa</creatorcontrib><creatorcontrib>Reichman, Sacha</creatorcontrib><creatorcontrib>Duebel, Jens</creatorcontrib><creatorcontrib>Sahel, Jose-Alain</creatorcontrib><creatorcontrib>Goureau, Olivier</creatorcontrib><creatorcontrib>Dalkara, Deniz</creatorcontrib><title>AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vectors based on adeno-associated virus (AAV) have shown the ability for gene delivery to retinal organoids derived from hiPSCs. Thus far, little work has been carried out to investigate mechanisms of AAV-mediated gene delivery and the potential advantages of engineered AAVs to genetically modify retinal organoids. In this study, we compared the early transduction efficiency of several recombinant and engineered AAVs in hiPSC-derived RPE cells and retinal organoids in relation to the availability of their cell-surface receptors and as a function of time. The genetic variant AAV2-7m8 had a superior transduction efficiency when applied at day 44 of differentiation on retinal organoids and provided long-lasting expressions for at least 4 weeks after infection without compromising cell viability. All of the capsids we tested transduced the hiPSC-RPE cells, with the AAV2-7m8 variant being the most efficient. Transduction efficiency was correlated with the presence of primary cell-surface receptors on the hiPS-derived organoids. Our study explores some of the mechanisms of cell attachment of AAVs and reports long-term gene expression resulting from gene delivery in retinal organoids.</description><subject>Biotechnology</subject><subject>Capsids</subject><subject>Cell adhesion</subject><subject>Cell cycle</subject><subject>Cell surface</subject><subject>Cell viability</subject><subject>Degenerative diseases</subject><subject>Efficiency</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Genetic diversity</subject><subject>Genetic modification</subject><subject>Heparan sulfate</subject><subject>Human health and pathology</subject><subject>Infections</subject><subject>Life Sciences</subject><subject>Organoids</subject><subject>Peptides</subject><subject>Photoreceptors</subject><subject>Pluripotency</subject><subject>Receptor mechanisms</subject><subject>Retina</subject><subject>Retinal degeneration</subject><subject>Sensory Organs</subject><subject>Stem cells</subject><subject>Transduction</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctr3DAQxkVISdK0t5yDIJcW6kZvW5fAsmmzgQ0pfV2FbI0TLba1leyF_PfVsmnY5qRh5qdvHh9CZ5R85lyTS7_qE6OEE63FATqhgrGCEFUe7sXH6G1KK0IYZ1IfoWPOCKtkJU-Qm81-F3fgvB3B4RsYAF9D5zcQn_AYML_G32H0g-3wfXywQ_AuZSBmwOE2hh4vpt4O-HZwU5NT37op-nUYYRjxjxF6PIeuS-_Qm9Z2Cd4_v6fo19cvP-eLYnl_czufLYtGVHosWiIVqMqVQkoiXM3qVtdQa6ZV6ZwA6spayAZayxtpWalkzUstKJWElo3U_BRd7XTXU92Da_IU0XZmHX1v45MJ1pv_K4N_NA9hY0rCVUVFFvi4E3h89W0xW5ptjjDJK0HUhmb2w3OzGP5MkEbT-9Tkde0AYUqGcckUF1SqjF68QldhivmomZKiyhRh2-afdlQTQ0oR2pcJKDFbq82-1Rk_31_2Bf7nLf8LCJGjQQ</recordid><startdate>20200203</startdate><enddate>20200203</enddate><creator>Garita-Hernandez, Marcela</creator><creator>Routet, Fiona</creator><creator>Guibbal, Laure</creator><creator>Khabou, Hanen</creator><creator>Toualbi, Lyes</creator><creator>Riancho, Luisa</creator><creator>Reichman, Sacha</creator><creator>Duebel, Jens</creator><creator>Sahel, Jose-Alain</creator><creator>Goureau, Olivier</creator><creator>Dalkara, Deniz</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4311-138X</orcidid><orcidid>https://orcid.org/0000-0002-7973-8301</orcidid><orcidid>https://orcid.org/0000-0003-1776-6339</orcidid><orcidid>https://orcid.org/0000-0003-0972-2117</orcidid><orcidid>https://orcid.org/0000-0003-4112-9321</orcidid><orcidid>https://orcid.org/0000-0002-4831-1153</orcidid></search><sort><creationdate>20200203</creationdate><title>AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells</title><author>Garita-Hernandez, Marcela ; Routet, Fiona ; Guibbal, Laure ; Khabou, Hanen ; Toualbi, Lyes ; Riancho, Luisa ; Reichman, Sacha ; Duebel, Jens ; Sahel, Jose-Alain ; Goureau, Olivier ; Dalkara, Deniz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-f056e68d745504db2bf9beb92967dd4e1d7b45cefa3c5a2765b3794115017c593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biotechnology</topic><topic>Capsids</topic><topic>Cell adhesion</topic><topic>Cell cycle</topic><topic>Cell surface</topic><topic>Cell viability</topic><topic>Degenerative diseases</topic><topic>Efficiency</topic><topic>Gene expression</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Genetic diversity</topic><topic>Genetic modification</topic><topic>Heparan sulfate</topic><topic>Human health and pathology</topic><topic>Infections</topic><topic>Life Sciences</topic><topic>Organoids</topic><topic>Peptides</topic><topic>Photoreceptors</topic><topic>Pluripotency</topic><topic>Receptor mechanisms</topic><topic>Retina</topic><topic>Retinal degeneration</topic><topic>Sensory Organs</topic><topic>Stem cells</topic><topic>Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garita-Hernandez, Marcela</creatorcontrib><creatorcontrib>Routet, Fiona</creatorcontrib><creatorcontrib>Guibbal, Laure</creatorcontrib><creatorcontrib>Khabou, Hanen</creatorcontrib><creatorcontrib>Toualbi, Lyes</creatorcontrib><creatorcontrib>Riancho, Luisa</creatorcontrib><creatorcontrib>Reichman, Sacha</creatorcontrib><creatorcontrib>Duebel, Jens</creatorcontrib><creatorcontrib>Sahel, Jose-Alain</creatorcontrib><creatorcontrib>Goureau, Olivier</creatorcontrib><creatorcontrib>Dalkara, Deniz</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garita-Hernandez, Marcela</au><au>Routet, Fiona</au><au>Guibbal, Laure</au><au>Khabou, Hanen</au><au>Toualbi, Lyes</au><au>Riancho, Luisa</au><au>Reichman, Sacha</au><au>Duebel, Jens</au><au>Sahel, Jose-Alain</au><au>Goureau, Olivier</au><au>Dalkara, Deniz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-02-03</date><risdate>2020</risdate><volume>21</volume><issue>3</issue><spage>994</spage><pages>994-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vectors based on adeno-associated virus (AAV) have shown the ability for gene delivery to retinal organoids derived from hiPSCs. Thus far, little work has been carried out to investigate mechanisms of AAV-mediated gene delivery and the potential advantages of engineered AAVs to genetically modify retinal organoids. In this study, we compared the early transduction efficiency of several recombinant and engineered AAVs in hiPSC-derived RPE cells and retinal organoids in relation to the availability of their cell-surface receptors and as a function of time. The genetic variant AAV2-7m8 had a superior transduction efficiency when applied at day 44 of differentiation on retinal organoids and provided long-lasting expressions for at least 4 weeks after infection without compromising cell viability. All of the capsids we tested transduced the hiPSC-RPE cells, with the AAV2-7m8 variant being the most efficient. Transduction efficiency was correlated with the presence of primary cell-surface receptors on the hiPS-derived organoids. Our study explores some of the mechanisms of cell attachment of AAVs and reports long-term gene expression resulting from gene delivery in retinal organoids.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32028585</pmid><doi>10.3390/ijms21030994</doi><orcidid>https://orcid.org/0000-0002-4311-138X</orcidid><orcidid>https://orcid.org/0000-0002-7973-8301</orcidid><orcidid>https://orcid.org/0000-0003-1776-6339</orcidid><orcidid>https://orcid.org/0000-0003-0972-2117</orcidid><orcidid>https://orcid.org/0000-0003-4112-9321</orcidid><orcidid>https://orcid.org/0000-0002-4831-1153</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2020-02, Vol.21 (3), p.994 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7036814 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biotechnology Capsids Cell adhesion Cell cycle Cell surface Cell viability Degenerative diseases Efficiency Gene expression Gene therapy Gene transfer Genetic diversity Genetic modification Heparan sulfate Human health and pathology Infections Life Sciences Organoids Peptides Photoreceptors Pluripotency Receptor mechanisms Retina Retinal degeneration Sensory Organs Stem cells Transduction |
| title | AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T21%3A14%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AAV-Mediated%20Gene%20Delivery%20to%203D%20Retinal%20Organoids%20Derived%20from%20Human%20Induced%20Pluripotent%20Stem%20Cells&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Garita-Hernandez,%20Marcela&rft.date=2020-02-03&rft.volume=21&rft.issue=3&rft.spage=994&rft.pages=994-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms21030994&rft_dat=%3Cproquest_pubme%3E2548634024%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2548634024&rft_id=info:pmid/32028585&rfr_iscdi=true |