A new strategy improves the efficiency of CRISPR-Cas9 genome editing

The effectiveness of the CRISPR genome editing tools targeted at the site of interest by Cas9 nucleases varies widely and a new CMP fusion strategy, called CRISPR-chrom, boosts activity until several times. CRISPR-chrom works by fusing a Cas9 with chromatin modulating peptides (CMPs), as described in an article published in CRISPR Newspaper.

In the article titled "Improving the efficiency of editing the CRISPR-Cas9 genome by fusing with chromatin-modulating peptides", Fuqiang Chen and a team of researchers from MilliporeSigma (St. Louis , MO) present the methods used to modify Cas9 with known peptides to naturally interact with chromatin, the DNA / RNA / protein complex that includes chromosomes. The researchers demonstrate a substantial increase in CRISPR-Cas9 activity with the CRISPR-chrom strategy, particularly on sites previously difficult to target. They also reported no noticeable increase in out-of-target effects. The authors also provided proof of concept for this approach using orthogonal Cas9 proteins to the well-known SpyCas9, further developing the CRISPR toolbox and also opening up new multiplexing capabilities.

"This is a notable technical improvement for an improved CRISPR toolkit," says Rodolphe Barrangou, Ph.D., editor of CRISPR Newspaper. "This approach improves the results of editing on refractory sites, and CRISPR-chrom, coupled with improved scaffolds, enhances our ability to genetically target the genome."

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More information:
Xiao Ding et al., Improving the efficiency of CRISPR-Cas9 genome editing by fusion with chromatin-modulating peptides, CRISPR Newspaper (2019). DOI: 10.1089 / CRISPR.2018.0036