Engineered CRISPR RNA improves the RNA cleavage efficiency of hfCas13X.

Autor: Liu Z; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Zhang W; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Wang H; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Shangguan P; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Pan T; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Yang Y; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Zhang Y; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Mao X; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Liu Y; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China., Zhang Q; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Oct; Vol. 598 (19), pp. 2438-2449. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1002/1873-3468.15025
Abstrakt: As the most compact variant in the Cas13 family, CRISPR-Cas13X holds considerable promise for gene therapy applications. The development of high-fidelity Cas13X (hfCas13X) mutants has enhanced the safety profile for in vivo applications. However, a notable reduction in on-target cleavage efficiency accompanies the diminished collateral cleavage activity in hfCas13X. In this study, we obtained two engineered crRNA mutants that notably enhance the on-target cleavage efficiency of hfCas13X. Furthermore, we have identified a novel crRNA structure that consistently augments the on-target cleavage efficiency of hfCas13X across various cellular environments, without significant enhancement of its collateral activity. These findings collectively enrich the gene-editing toolkit, presenting a more effective hfCas13X system for future research and application.
(© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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