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New modified CRISPR protein can fit inside virus used for gene therapy

Date: 5.6.2024 

Researchers have developed a novel version of a key CRISPR gene-editing protein that shows efficient editing activity and is small enough to be packaged within a non-pathogenic virus that can deliver it to target cells.

Kredit: Chen Peng, CC BY-SA 4.0.Hongjian Wang and colleagues at Wuhan University, China, present these findings in the open-access journal PLOS Biology.

Recent years have seen an explosion of research attempting to harness CRISPR gene-editing systems. One promising idea is to package CRISPR proteins within a non-pathogenic virus, which could then deliver the proteins to target cells; there, they would modify specifically targeted DNA sequences to treat disease. However, the commonly used adeno-associated virus is small, and while some Cas9 proteins can fit inside, Cas12a proteins are typically too large.

Now, Wang and colleagues have identified a relatively small version of Cas12a, termed EbCas12a, that occurs naturally in a species of the Erysipelotrichia class of bacteria. By deliberately switching out one of the amino acid building blocks of the protein for another, they boosted its gene-editing efficiency.

When applied to mammalian cells in a dish in the lab, this modified protein – dubbed enEbCas12a – shows gene-editing efficiency comparable to that of two other Cas12a proteins known for highly accurate gene editing.

Image source: Chen PengCC BY-SA 4.0.





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