How human cells edit gene messages (RNA splicing)
Mechanisms of Gene Expression
Researchers are using precise CRISPR base editing in human cells to change single DNA letters and find parts of the splicing machinery that affect how gene messages are assembled.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11252314 on NIH RePORTER |
What this research studies
The team uses CRISPR base editors to introduce point mutations across hundreds of spliceosome proteins in haploid human cell lines. They treat the edited cells with a splicing-targeting drug (pladienolide B) and sequence survivors to pinpoint edits that alter drug response. This approach highlights specific protein sites and human-only spliceosomal factors, including unexpected hits like SUGP1. All work is lab-based in human cells and aims to map components that control normal and disease-related RNA splicing.
Who could benefit from this research
Good fit: Patients most likely to benefit in the future are those with genetic disorders or cancers caused by abnormal RNA splicing.
Not a fit: Patients with conditions unrelated to RNA splicing or who need immediate clinical care are unlikely to receive direct benefit from this basic laboratory research.
Why it matters
Potential benefit: If successful, this work could reveal human-specific spliceosome targets that lead to new diagnostics or treatments for diseases driven by abnormal RNA splicing.
How similar studies have performed: CRISPR base editing and yeast genetics have previously helped map splicing components, but systematically applying base editors across the human spliceosome in haploid human cells is a newer and less-tested approach.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Madhani, Hiten D — University of California, San Francisco
- Study coordinator: Madhani, Hiten D
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.