Finding and improving short RNA guides to correct single-letter gene errors
High-throughput screening and structure-guided optimization of oligonucleotides for site-directed RNA editing by ADARs.
This project develops short RNA guides that steer a natural enzyme to change a single-letter error in a person's mRNA so a faulty protein can be made correctly.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California at Davis NIH-funded |
| Lab location | 1 site (Davis, United States) |
| Project ID | NIH-11349640 on NIH RePORTER |
What this research studies
Scientists will create and test thousands of short guide RNAs to pair with a target mRNA and recruit the natural ADAR enzyme to change one adenosine into an inosine, which the cell reads as guanosine. They will use high-throughput screening to find guide sequences that produce strong, specific editing of disease-causing stop codons and apply structural information to improve the best guides. Experiments will be carried out in cells and biochemical systems to measure how well each guide edits the intended site and to check for unwanted edits elsewhere. The team aims to produce optimized guide oligonucleotides that could be adapted toward future therapies for genetic disorders caused by single-point mutations.
Who could benefit from this research
Good fit: People whose condition is caused by a single-point adenosine mutation—for example a nonsense mutation that creates a premature stop codon—would be the primary candidates for therapies developed from this work.
Not a fit: Patients with large deletions, complex structural mutations, non-adenosine-based errors, or non-genetic conditions are unlikely to benefit from an A-to-I RNA editing approach.
Why it matters
Potential benefit: If successful, this approach could restore full-length functional proteins for people with certain single-letter genetic mutations, potentially reducing disease symptoms.
How similar studies have performed: Laboratory and some animal studies have shown proof-of-concept that ADAR-directed editing can correct specific mRNA sites, but reliable, safe therapeutic translation remains early-stage.
Where this research is happening
Davis, United States
- University of California at Davis — Davis, United States (Active)
Researchers
- Principal investigator: Fisher, Andrew J — University of California at Davis
- Study coordinator: Fisher, Andrew J
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.