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In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.

ABSTRACT: We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the specificity and activity of the toolsets in vitro and in vivo via two mouse models of human disease. We anticipate that this platform will enable tunable and reversible engineering of cellular RNAs for diverse applications.

SUBMITTER: Katrekar D 

PROVIDER: S-EPMC6395520 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.

Katrekar Dhruva D   Chen Genghao G   Meluzzi Dario D   Ganesh Ashwin A   Worlikar Atharv A   Shih Yu-Ru YR   Varghese Shyni S   Mali Prashant P  

Nature methods 20190208 3

We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the specificity and activity of the toolsets in vitro and in vivo via two mouse models of human disease. We anticipate that this platform will enable tunable and reversible engineering of cellular RNAs for diverse applications. ...[more]

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