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.
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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-pp.ucl.ac.uk/id/eprint/10047345 |
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