RARE Daily

Penn Patents New Gene-Editing Technique to Turn on Enzymes That Cause Base Mutations

October 29, 2021

Targeted mutations to the genome can now be introduced by splitting specific mutator enzymes and then triggering them to reconstitute, according to research from the Perelman School of Medicine at the University of Pennsylvania.

Led by graduate student Kiara Berríos, researchers uncovered a novel gene editing technique that offers what they said was superior control compared to other existing techniques and has the potential to be used in vivo. The technique has been patented, and the research is published in the latest issue of Nature Chemical Biology.

Base editors are one of the latest and most effective ways to achieve precise gene editing. In DNA targeted by base editors, C:G base pairs in DNA can be mutated to T:A or A:T base pairs can be turned to G:C. The base editors use CRISPR-Cas proteins to locate a specific DNA target and DNA deaminase enzymes to modify and mutate the target. However, the researchers said there was no way to trigger mutations at specific times or keep the editor in check to prevent undesired mutations.

The Penn researchers found that DNA deaminases can be divided into two inactive pieces, which can then be put back together using a small cell-permeable molecule called rapamycin. The new split-engineered base editors (seBEs) system can be introduced and lay dormant within a cell until the small molecule is added, at which point the base editing complex can be rapidly “turned on” to alter the genome.

The technique may also have potential in controlling genetic changes that cause cancer development and growth. It could also be used to identify vulnerabilities in cancer cells, the researchers said.

“Our newly created split-engineered base editors really offer new potential for both research and therapeutics,” said Rahul Kohli, an assistant professor of Cancer Biology at Penn and supervisor of the research. “Since we can control the time mutations are made, there is a possibility to use these seBEs in vivo to model diseases by altering a gene, similar to how scientists control the timing of gene knockouts, and even potentially someday offer clinicians the ability to control editing of a patient’s genes for treatment purposes.”

Photo: Kiara Berríos, graduate student who led the research

Author: Rare Daily Staff

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