Home News Harvard Scientists Pioneer HACE, a New Technique for Targeted Gene Mutation in Human Cells

Harvard Scientists Pioneer HACE, a New Technique for Targeted Gene Mutation in Human Cells

Delving into the intricate dance of DNA, Harvard researchers have introduced a trailblazing technique that boasts the ability to orchestrate gene mutations within living human cells. As reported in Science, the innovation, branded Helicase-Assisted Continuous Editing (HACE), provides scientists an avenue to focus mutations exclusively on genes of particular interest, thus untangling some of the complexities in genetic research.

The human genome, a sprawling map of 3 billion base pairs and thousands of genes, has long posed as a challenge for targeted genetic manipulation. HACE, however, sidesteps this obstacle by allowing mutations to be made at specified regions without disrupting the genome’s overall integrity. Xi Dawn Chen, a Griffin Graduate School of Arts and Sciences student at Harvard, told

Harvard Gazette

, “By allowing targeted mutagenesis in specific parts of the genome, this tool opens the door to creating enzymes and treatments that were previously out of reach.”

The novelty of HACE lies in its ensemble of a helicase, known for unwinding DNA strands, alongside a gene-editing enzyme, which then pairs with CRISPR-Cas9 technology to hone in on the desired gene sequences. “HACE combines CRISPR’s precision with the ability to edit long stretches of DNA, making it a powerful tool for targeted evolution,” Professor Fei Chen of Harvard described in a statement, affirming the significance of their method in the realm of genetic engineering, as per

Harvard Gazette

.

To showcase HACE’s prowess, the Harvard team put the tool to test against the MEK1 gene—a common target for certain cancer treatments. They succeeded in isolating resistance mutations linked to drug performance, particularly against medications such as trametinib and selumetinib. Additionally, the team used HACE to scrutinize mutations in the SF3B1 gene, a key player in the RNA splicing process and a suspect in blood cancers. In a collaborative effort with Bradley Bernstein’s lab at Harvard Medical School and Dana-Farber Cancer Institute, HACE also paved the way for a better grasp on how DNA regulatory regions impact protein production in immune cells, shedding light on potential cancer immunotherapies.

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As

Harvard Gazette

notes, the support for this research was broad, with contributions from entities such as the National Institutes of Health, the Broad Institute, and the Harvard Stem Cell Institute. With this new foray into precise genetic editing, therapeutic opportunities that hinge on “fixing” gene activity to treat diseases seem closer within reach, according to Bernstein. While transforming the genetic landscape, HACE holds promise for unraveling the complexities of human diseases and potentially ushering in new avenues for drug discovery and treatment.

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