衣壳
核糖核酸
适体
核糖核蛋白
计算生物学
分子生物学
生物
化学
病毒学
基因
遗传学
病毒
作者
Pin Lyu,Zuyan Lu,Sung-Ik Cho,Manish Kumar Yadav,Kyung Whan Yoo,Anthony Atala,Jin-Soo Kim
出处
期刊:The CRISPR journal
[Mary Ann Liebert]
日期:2021-02-01
卷期号:4 (1): 69-81
被引量:21
标识
DOI:10.1089/crispr.2020.0095
摘要
Adenine base editors (ABEs) can correct gene mutations without creating double-strand breaks. However, in recent reports, these editors showed guide-independent RNA off-target activities. This work describes our development of a delivery method to minimize ABEs' RNA off-target activity. After discovering a RNA off-target hot spot for sensitive detection of RNA off-target activities, we found that delivering ribonucleoproteins (RNPs) by electroporation generated undetectable non-specific RNA editing, but on-target base editing activity was also relatively low. We then explored a lentivirus capsid-based delivery strategy to deliver ABE. We used aptamer/aptamer-binding protein (ABP) interactions to package ABE RNPs into lentiviral capsids. Capsid RNPs were delivered to human cells for highly efficient guided base editing. Importantly, RNA off-target activities from the capsid RNPs were undetectable. Our new lentiviral capsid-based ABE RNP delivery method with minimal RNA off-target activities makes ABE one step closer to possible therapeutic applications.
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