BROWSE

Related Scientist

GEL's photo.

GEL
유전체 교정 연구단
more info

ITEM VIEW & DOWNLOAD

Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA

Cited 0 time in webofscience Cited 0 time in scopus
61 Viewed 0 Downloaded
Title
Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA
Author(s)
Sung-Ik Cho; Kayeong Lim; Hong, Seongho; Jaesuk Lee; Annie Kim; Lim, Chae Jin; Ryou, Seungmin; Ji Min Lee; Young Geun Mok; Eugene Chung; Kim, Sanghun; Han, Seunghun; Cho, Sang-Mi; Kim, Jieun; Kim, Eun-Kyoung; Nam, Ki-Hoan; Oh, Yeji; Minkyung Choi; An, Tae Hyeon; Oh, Kyoung-Jin; Seonghyun Lee; Hyun Ji Lee; Jin Soo Kim
Publication Date
2024-01
Journal
Cell, v.187, no.1, pp.95 - 109.e26
Publisher
Elsevier B.V.
Abstract
DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates. © 2023 The Authors
URI
https://pr.ibs.re.kr/handle/8788114/14719
DOI
10.1016/j.cell.2023.11.035
ISSN
0092-8674
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
There are no files associated with this item.

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse