Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice

Pengpeng Liu, Shun-Qing Liang, Chunwei Zheng, Esther Mintzer, Yan G. Zhao, Karthikeyan Ponnienselvan, Aamir Mir, Erik J. Sontheimer, Guangping Gao, Terence R. Flotte, Scot A. Wolfe () and Wen Xue ()
Additional contact information
Pengpeng Liu: University of Massachusetts Medical School
Shun-Qing Liang: University of Massachusetts Medical School
Chunwei Zheng: University of Massachusetts Medical School
Esther Mintzer: University of Massachusetts Medical School
Yan G. Zhao: University of Massachusetts Medical School
Karthikeyan Ponnienselvan: University of Massachusetts Medical School
Aamir Mir: University of Massachusetts Medical School
Erik J. Sontheimer: University of Massachusetts Medical School
Guangping Gao: University of Massachusetts Medical School
Terence R. Flotte: University of Massachusetts Medical School
Scot A. Wolfe: University of Massachusetts Medical School
Wen Xue: University of Massachusetts Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Here we report an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency in both fluorescent reporter cells and at endogenous loci in cultured cell lines. Using this genome modification system, we could also seed tumor formation through somatic cell editing in the adult mouse. Finally, we successfully utilize dual adeno-associated virus (AAVs) for the delivery of a split-intein prime editor and demonstrate that this system enables the correction of a pathogenic mutation in the mouse liver. Our findings further establish the broad potential of this genome editing technology for the directed installation of sequence modifications in vivo, with important implications for disease modeling and correction.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (11)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22295-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22295-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22295-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().