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Harvard researchers have unveiled Helicase-Assisted Continuous Editing (HACE), a cutting-edge tool that enables precise genetic modifications in specific regions of the human genome without altering other areas. This innovation combines CRISPR-Cas9 gene-editing technology with helicase, a DNA-unzipping enzyme, allowing scientists to focus mutations on target genes. Such precision facilitates studying how gene mutations contribute to diseases and could drive the development of new therapies.
Described in the journal Science, HACE has been used to uncover mutations that enable cancer cells to resist treatment. For example, the team identified changes in the MEK1 gene, which helps explain why certain drugs lose effectiveness against cancer. They also explored mutations in SF3B1, a gene implicated in blood cancers, revealing how these changes disrupt RNA processing.
The tool also helped uncover how mutations in SF3B1, a gene involved in RNA splicing, disrupt RNA assembly—a common problem in blood cancers. Additionally, in collaboration with Harvard Medical School and Dana-Farber Cancer Institute, researchers used HACE to explore regulatory DNA changes that influence immune cell proteins, revealing potential targets for cancer immunotherapy.
According to Fei Chen, the study’s senior author, HACE combines the precision of CRISPR with the ability to edit extensive DNA sequences, offering unparalleled control over targeted mutations. Bradley Bernstein, a collaborator, suggested that such tools could one day allow precise tuning of gene regulatory sequences, unlocking new therapeutic possibilities. HACE represents a transformative step in understanding evolution, gene regulation, and disease mechanisms.
