Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope
Name
s41467-020-15892-8.pdf
Description
Published version
Size
1.18 MB
Format
Unknown
Checksum (MD5)
bc007ea4c9e7846722e0bb3a3ff48af0
Author(s)
Jiang, Tingting
Henderson, Jordana M.
Coote, Kevin
Cheng, Yi
Valley, Hillary C.
Zhang, Xiao-Ou
Wang, Qin
Rhym, Luke H.
Cao, Yueying
Newby, Gregory A.
Date Issued
April 2020
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2020, The Author(s). CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base editing requires cellular exposure to levels of base editors that can be difficult to attain in hard-to-transfect cells or in vivo. Here we engineer a chemically modified mRNA-encoded adenine base editor that mediates robust editing at various cellular genomic sites together with moderately modified guide RNA, and show its therapeutic potential in correcting pathogenic single nucleotide mutations in cell and animal models of diseases. The optimized chemical modifications of adenine base editor mRNA and guide RNA expand the applicability of CRISPR-associated gene editing tools in vitro and in vivo.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41467-020-15892-8
