A new method to change large stretches of genes to find DNA switches and drug resistance
Multiplexed Locus-Specific Hypermutation for Functional Characterization of the Coding and Noncoding Genome
This project develops a lab method that makes many small DNA changes across large parts of human genes to find DNA regions that control gene activity and how cancers can become resistant to drugs.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Broad Institute, INC. NIH-funded |
| Lab location | 1 site (Cambridge, United States) |
| Project ID | NIH-11257305 on NIH RePORTER |
What this research studies
From my perspective as a patient, researchers are building a tool called HACE that can continuously introduce mutations across long stretches of DNA in human cells. They link a helicase enzyme to a DNA-changing enzyme and guide it to specific gene regions using a modified CRISPR system so many nearby bases can be altered. The team will use this approach to map noncoding regulatory DNA that turns genes on or off and to probe the MEK signaling pathway to see how cells develop resistance to small-molecule cancer drugs. This work happens in the lab using cell models and genomic sequencing rather than in people directly.
Who could benefit from this research
Good fit: People with cancers involving the MEK pathway or patients willing to contribute tumor samples for laboratory research would be most relevant to this work.
Not a fit: Patients seeking immediate clinical treatment or those with conditions unrelated to gene regulation or MEK signaling are unlikely to benefit directly from this lab-focused project.
Why it matters
Potential benefit: If successful, this could help scientists pinpoint DNA switches and drug-resistance mechanisms that lead to better-targeted treatments or ways to prevent resistance.
How similar studies have performed: Related genome-editing and directed-evolution tools have worked in cells, but this long-range, continuous mutagenesis approach is novel and has not yet been proven in clinical settings.
Where this research is happening
Cambridge, United States
- Broad Institute, INC. — Cambridge, United States (Active)
Researchers
- Principal investigator: Chen, Fei — Broad Institute, INC.
- Study coordinator: Chen, Fei
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.