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Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells

Gonzalez Cordero, A; Goh, D; Kruczek, K; Naeem, A; Fernando, M; Kleine Holthaus, S-M; Takaaki, M; ... Ali, RR; + view all (2018) Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells. Human Gene Therapy , 29 (10) pp. 1124-1139. 10.1089/hum.2018.027. Green open access

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Abstract

Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem-cell derived retina now offers the possibility to assess efficacy in human organoids in vitro. Here we test 6 AAV serotypes (AAV2/2, AAV2/9, AAV2/8, AAV2/8T(Y733F), AAV2/5 and ShH10) to determine their efficiency in transducing mouse and human pluripotent stem cell (PSC)-derived RPE and photoreceptor cells in vitro. All the serotypes tested were capable of transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and ShH10 achieved similarly robust transduction of human ESC-derived cone photoreceptors. Furthermore, we show that hESC-derived photoreceptors can be used to establish promoter specificity in human cells in vitro. The results of this study will aid capsid selection and vector design for pre-clinical evaluation of gene therapy approaches, such as gene editing, that require the use of human cells and tissues.

Type: Article
Title: Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/hum.2018.027
Publisher version: https://doi.org/10.1089/hum.2018.027
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: pluripotent stem cells; retinal organoids; AAV serotypes; gene therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10047345
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