Development of Highly Efficient Dual‐AAV Split Adenosine Base Editor for In Vivo Gene Therapy
Abstract: The adenosine base editor (ABE) is able to catalyze A•T to C•G conversion efficiently and precisely in vivo, representing a new method for gene therapy. Adeno associated virus (AAV) is a well‐studied vector for gene delivery in vivo. However, due to the limited loading capacity of AAV vector (≈4800 bp), it is difficult to package ABE (≈5400 bp) into a single AAV. To tackle this problem, ABE can be split into two smaller parts through intein‐mediated protein trans‐splicing. Here, 14 different split sites of nCas9 (Cas9 nickase) in combination with three different inteins (Mxe, Npu, and Rma) are screened through a GFP‐based reporter system to identify novel split‐ABEs. After infecting HEK293T and HeLa cells with dual AAVs, two split‐ABEs (split‐ABE‐Rma573 and split‐ABE‐Rma674) that can edit the target gene efficiently are identified. Furthermore, these dual‐AAV split‐ABEs can effectively disrupt the splicing acceptor of PCSK9 in mouse liver and the splicing donor of NR2E3 in mouse retina through AI‐MAST strategy. This study provides two new split‐ABEs to investigate gene function in vivo and in gene therapy, representing a new method to treat diseases by precisely repairing point mutations or inactivating genes through the AI‐MAST strategy.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Development of Highly Efficient Dual‐AAV Split Adenosine Base Editor for In Vivo Gene Therapy ; volume:4 ; number:9 ; year:2020 ; extent:13
Small Methods ; 4, Heft 9 (2020) (gesamt 13)
- Urheber
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Chen, Yuxi
Zhi, Shengyao
Liu, Weiliang
Wen, Jinkun
Hu, Sihui
Cao, Tianqi
Sun, Hongwei
Li, Yang
Huang, Li
Liu, Yizhi
Liang, Puping
Huang, Junjiu
- DOI
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10.1002/smtd.202000309
- URN
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urn:nbn:de:101:1-2022060807032483986073
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:28 MESZ
Datenpartner
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Beteiligte
- Chen, Yuxi
- Zhi, Shengyao
- Liu, Weiliang
- Wen, Jinkun
- Hu, Sihui
- Cao, Tianqi
- Sun, Hongwei
- Li, Yang
- Huang, Li
- Liu, Yizhi
- Liang, Puping
- Huang, Junjiu
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