Zhang, Nan and Bewick, Brittani and Xia, Guangbin and Furling, Denis and Ashizawa, Tetsuo (2020) A CRISPR-Cas13a Based Strategy That Tracks and Degrades Toxic RNA in Myotonic Dystrophy Type 1. Frontiers in Genetics, 11. ISSN 1664-8021
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Abstract
Cas13a, an effector of type VI CRISPR-Cas systems, is an RNA guided RNase with multiplexing and therapeutic potential. This study employs the Leptotrichia shahii (Lsh) Cas13a and a repeat-based CRISPR RNA (crRNA) to track and eliminate toxic RNA aggregates in myotonic dystrophy type 1 (DM1) – a neuromuscular disease caused by CTG expansion in the DMPK gene. We demonstrate that LshCas13a cleaves CUG repeat RNA in biochemical assays and reduces toxic RNA load in patient-derived myoblasts. As a result, LshCas13a reverses the characteristic adult-to-embryonic missplicing events in several key genes that contribute to DM1 phenotype. The deactivated LshCas13a can further be repurposed to track RNA-rich organelles within cells. Our data highlights the reprogrammability of LshCas13a and the possible use of Cas13a to target expanded repeat sequences in microsatellite expansion diseases.
Item Type: | Article |
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Subjects: | STM Digital > Medical Science |
Depositing User: | Unnamed user with email support@stmdigital.org |
Date Deposited: | 25 Jan 2023 11:24 |
Last Modified: | 11 Jul 2024 10:49 |
URI: | http://research.asianarticleeprint.com/id/eprint/88 |