Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing

Minh Thuan Nguyen Tran; Mohd Khairul Nizam Mohd Khalid; Qi Wang; Jacqueline K. R. Walker; Grace E. Lidgerwood; Kimberley L. Dilworth; Leszek Lisowski; Alice Pébay; Alex W. Hewitt

doi:10.1038/s41467-020-18715-y

Nature Communications (Sep 2020)

Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing

Minh Thuan Nguyen Tran,
Mohd Khairul Nizam Mohd Khalid,
Qi Wang,
Jacqueline K. R. Walker,
Grace E. Lidgerwood,
Kimberley L. Dilworth,
Leszek Lisowski,
Alice Pébay,
Alex W. Hewitt

Affiliations

Minh Thuan Nguyen Tran: Menzies Institute for Medical Research, School of Medicine, University of Tasmania
Mohd Khairul Nizam Mohd Khalid: Menzies Institute for Medical Research, School of Medicine, University of Tasmania
Qi Wang: Menzies Institute for Medical Research, School of Medicine, University of Tasmania
Jacqueline K. R. Walker: Menzies Institute for Medical Research, School of Medicine, University of Tasmania
Grace E. Lidgerwood: Department of Surgery, The University of Melbourne
Kimberley L. Dilworth: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney
Leszek Lisowski: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney
Alice Pébay: Department of Surgery, The University of Melbourne
Alex W. Hewitt: Menzies Institute for Medical Research, School of Medicine, University of Tasmania

DOI: https://doi.org/10.1038/s41467-020-18715-y
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 10

Abstract

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Off-target effects and the feasibility for AAV-mediated delivery are the major barriers impeding the clinical in vivo application of base editors. Here, the authors report the small size AAV-deliverable Cas9-ABE variant that has improved on-target editing efficiency and reduced RNA-off target footprint.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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