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Gene-editing enzymes imaged in 3D

July 8 (UPI) — Scientists have for the first time captured high-definition, 3D images of enzymes in the process of cutting DNA strands.

The breakthrough — described Monday in the journal Nature Structural and Molecular Biology — helped scientists see exactly how the gene-editing technology called CRISPR-Cas9 works, and could, in the future, help researchers design a more efficient and precise version of the technology.

The findings could also help scientists better understand — and eventually, treat and prevent — diseases caused by DNA mutations, including cancer, sickle cell anemia, Tay-Sachs disease, Huntington’s disease and many others.

“It is exciting to be able to see at such a high level of detail how Cas9 actually works to cut and edit DNA strands,” lead study author Sriram Subramaniam, researcher at the University of British Columbia, said in a news release. “These images provide us with invaluable information to improve the efficiency of the gene-editing process so that we can hopefully correct disease-causing DNA mutations more quickly and precisely in the future.”

CRISPR-Cas9, or CRISPR for short, relies on the creation of double-strand breaks, or DSBs, in the genomic regions targeted for manipulation. CRISPR deploys enzymes that act as molecular scissors. Once the DNA is cut, the sequence can be altered.

But CRISPR isn’t perfect. Previous studies have shown the technology regularly creates unwanted mutations.

To better understand how CRISPR works, scientists deployed an imaging technique called cryogenic electron microscopy, or cryo-EM. The images revealed the step-by-step molecular movements during the DNA-cutting process.

“One of the main hurdles preventing the development of better gene-editing tools using Cas9 is that we didn’t have any images of it actually cutting DNA,” said University of Illinois researcher Miljan Simonovic, co-author of the new study. “But now we have a much clearer picture, and we even see how the major domains of the enzyme move during reaction and this may be an important target for modification.”

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