Enhancement of homology-directed repair with chromatin donor templates in cells

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Abstract

A key challenge in precise genome editing is the low efficiency of homology-directed repair (HDR). Here we describe a strategy for increasing the efficiency of HDR in cells by using a chromatin donor template instead of a naked DNA donor template. The use of chromatin, which is the natural form of DNA in the nucleus, increases the frequency of HDR-edited clones as well as homozygous editing. In addition, transfection of chromatin results in negligible cytotoxicity. These findings suggest that a chromatin donor template should be useful for a wide range of HDR applications such as the precise insertion or replacement of DNA fragments that contain the coding regions of genes.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

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Grisel Cruz-Becerra

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

Competing interests
Grisel Cruz-Becerra, has filed a patent application (PCT/US2019/029194) that describes the invention reported in this article.

"This ORCID iD identifies the author of this article:" 0000-0001-6297-4132
James T Kadonaga

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

For correspondence
jkadonaga@ucsd.edu

Competing interests
James T Kadonaga, has filed a patent application (PCT/US2019/029194) that describes the invention reported in this article.

"This ORCID iD identifies the author of this article:" 0000-0002-2075-9458

Funding

National Institutes of Health (R35 GM118060)

James T Kadonaga

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.