sgBE: a structure-guided design of sgRNA architecture specifies base editing window and enables simultaneous conversion of cytosine and adenosine.


Journal

Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660

Informations de publication

Date de publication:
28 08 2020
Historique:
received: 17 01 2020
accepted: 07 08 2020
entrez: 30 8 2020
pubmed: 30 8 2020
medline: 13 7 2021
Statut: epublish

Résumé

We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among tested sgBEs, sgBE-SL4, in which deaminase is attached to the last stem-loop of sgRNA, yields the highest editing efficiency in the window several nucleotides next to the one edited by BE3. sgBE enables the simultaneous editing of adenine and cytosine. Finally, in order to facilitate in vivo base editing, we extend our sgBE system to an AAV-compatible Cas9, SaCas9 (Staphylococcus aureus), and observe robust base editing.

Identifiants

pubmed: 32859244
doi: 10.1186/s13059-020-02137-6
pii: 10.1186/s13059-020-02137-6
pmc: PMC7453718
doi:

Substances chimiques

Nucleotides 0
RNA, Guide 0
Cytosine 8J337D1HZY
CRISPR-Associated Protein 9 EC 3.1.-
Adenine JAC85A2161
Adenosine K72T3FS567

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

222

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Auteurs

Yanhong Wang (Y)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Lifang Zhou (L)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Rui Tao (R)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Nan Liu (N)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Jie Long (J)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Fengming Qin (F)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Wenling Tang (W)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Yang Yang (Y)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Qiang Chen (Q)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China.

Shaohua Yao (S)

Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041, Sichuan, China. shaohuayao@scu.edu.cn.

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Classifications MeSH