Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors
In: JCI Insight, Jg. 4 (2019-11-14), Heft 22
Online
academicJournal
- e131610
While gene transfer using recombinant adeno-associated viral (rAAV) vectors has shown success in some clinical trials, there remain many tissues that are not well transduced. Because of the recent success in reprogramming islet-derived cells into functional β cells in animal models, we constructed 2 highly complex barcoded replication competent capsid shuffled libraries and selected for high-transducing variants on primary human islets. We describe the generation of a chimeric AAV capsid (AAV-KP1) that facilitates transduction of primary human islet cells and human embryonic stem cell-derived β cells with up to 10-fold higher efficiency compared with previously studied best-in-class AAV vectors. Remarkably, this chimeric capsid also enabled transduction of both mouse and human hepatocytes at very high levels in a humanized chimeric mouse model, thus providing a versatile vector that has the potential to be used in both preclinical testing and human clinical trials for liver-based diseases and diabetes.
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Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors
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Autor/in / Beteiligte Person: | Pekrun, Katja ; De Alencastro, Gustavo ; Luo, Qing-Jun ; Liu, Jun ; Kim, Youngjin ; Nygaard, Sean ; Galivo, Feorillo ; Zhang, Feijie ; Song, Ren ; Tiffany, Matthew R ; Xu, Jianpeng ; Hebrok, Matthias ; Grompe, Markus ; Kay, Mark A |
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Zeitschrift: | JCI Insight, Jg. 4 (2019-11-14), Heft 22 |
Veröffentlichung: | eScholarship, University of California, 2019 |
Medientyp: | academicJournal |
Umfang: | e131610 |
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