Next-level CRISPR gene editing: No viruses required and a new type of DNA repair

Good news! Incremental progress!

"... Viruses used for gene-editing purposes are expensive, hard to scale, and potentially toxic to cells. So the researchers looked at developing an alternative delivery method, adding interstrand crosslinks to the homology-directed repair template. ..."

"... a method that increases the efficiency of CRISPR/Cas9 editing without the use of viral material to deliver the genetic template used to edit the target genetic sequence. ... their method stimulates homology-directed repair (a step in the gene editing process) by approximately threefold “without increasing mutation frequencies or altering end-joining repair outcomes.” ..."

From the (very short) abstract:

"We describe a strategy to boost the efficiency of gene editing via homology-directed repair (HDR) by covalently modifying the template DNA with interstrand crosslinks. Crosslinked templates (xHDRTs) increase Cas9-mediated editing efficiencies by up to fivefold in K562, HEK293T, U2OS, iPS and primary T cells. Increased editing from xHDRTs is driven by events on the template molecule and requires ataxia telangiectasia and Rad3-related (ATR) kinase and components of the Fanconi anemia pathway."

Next-level CRISPR gene editing: No viruses required Modified viruses have proven a handy way to get CRISPR/Cas9 gene editing materials into the nucleus of cells – but they're expensive, difficult to scale and potentially toxic. Now, researchers have found a non-viral approach that does the job better.

Researchers discover a way to improve nonviral gene editing as well as a new type of DNA repair

Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells (open access)

Extended Data Fig. 1: Modification of HDRTs with interstrand crosslinks increases HR during gene editing.