Evaluating high-fidelity CRISPR-Cas nucleases in nucleosomal contexts using a quantitative framework

Christopher R. Handelmann, Erin Skeens, George P. Lisi, Michael J. Buck · 2026

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Description

Christopher Handelmann and co-authors test gene editing enzymes inside packed DNA in a study published in 2026. In cells, DNA wraps around proteins to form nucleosomes, which can block editing tools from reaching their targets. Many newer Cas enzymes cut with high care on bare DNA, but their behavior in this packed setting was unclear.

Using a profiling method called GEMiNI-seq, the team tested standard and engineered Cas9 and Cas12a enzymes across many nucleosome types. All enzymes cut less in packed DNA, most of all near the center of the wrap. One variant cut up to sixty-five times more on one nucleosome type than another. High-care variants often did poorly in packed DNA, so the team offers guidance for picking tools by context.

Catalog record

CREATORChristopher R. Handelmann, Erin Skeens, George P. Lisi, Michael J. Buck
YEAR2026
COLLECTIONPAPERS
FORMATTXT
FILE SIZE47 KB
VERSION1.0
LICENSECC BY 4.0
RIGHTSCC BY
SOURCEEurope PMC

Source: https://europepmc.org/articles/PMC13522198

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