Search-and-replace genome editing without double-strand breaks or donor DNA

Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, David R. Liu · Full author list: Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa, Luke W. Koblan, Jonathan M. Levy, Peter J. Chen, Christopher Wilson, Gregory A. Newby, Aditya Raguram, David R. Liu.

Published 21 October 2019 · Nature · Journal article

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Summary

This paper introduced prime editing, a versatile genome-editing method that uses a Cas9 nickase fused to a reverse transcriptase guided by a prime editing guide RNA (pegRNA) to write new genetic information directly into a target site. Without requiring double-strand breaks or donor DNA, prime editing can install targeted insertions, deletions, and all 12 types of point mutations. The authors demonstrated correction of disease-relevant mutations in human cells with broad targeting flexibility and relatively low off-target activity.

Key findings

Introduced prime editing using a Cas9 nickase-reverse transcriptase fusion plus a pegRNA template
Enabled targeted insertions, deletions, and all 12 possible point mutations without double-strand breaks or donor DNA
Corrected disease-associated mutations (e.g., sickle cell and Tay-Sachs alleles) in human cells

Subjects & keywords

Biology & Genetics prime editing crispr genome editing reverse transcriptase pegrna

Cite this paper

APA

Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, & David R. Liu [Full author list: Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa, Luke W. Koblan, Jonathan M. Levy, Peter J. Chen, Christopher Wilson, Gregory A. Newby, Aditya Raguram, David R. Liu.] (2019). Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. https://doi.org/10.1038/s41586-019-1711-4

BibTeX

@article{anzalone2019searchandreplace,
  author    = {Andrew V. Anzalone and Peyton B. Randolph and Jessie R. Davis and David R. Liu and {Full author list: Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa, Luke W. Koblan, Jonathan M. Levy, Peter J. Chen, Christopher Wilson, Gregory A. Newby, Aditya Raguram, David R. Liu.}},
  title     = {Search-and-replace genome editing without double-strand breaks or donor DNA},
  journal   = {Nature},
  year      = {2019},
  doi       = {10.1038/s41586-019-1711-4},
  url       = {https://doi.org/10.1038/s41586-019-1711-4}
}

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