Restoring SYNGAP1 protein by correcting RNA splicing
Rescuing SYNGAP1 haploinsufficiency by redirecting alternative splicing
This project aims to correct a faulty RNA splicing event to increase SYNGAP1 protein levels linked to SYNGAP1-related autism and intellectual disability.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Chicago NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project ID | NIH-11307079 on NIH RePORTER |
What this research studies
If you or your child has SYNGAP1-related autism, this project looks at a splicing error that causes SYNGAP1 messenger RNA to be destroyed and lowers protein levels. Researchers will use genetic methods and splice-switching oligonucleotides (SSOs) to block that splicing event in mouse models and in neurons made from patient-derived stem cells. They will test whether fixing the splicing change restores SYNGAP1 protein and improves measures of synaptic function in cells and animals. The work will create preclinical tools and knowledge needed to move toward treatments for people with SYNGAP1 haploinsufficiency.
Who could benefit from this research
Good fit: Ideal candidates are people with confirmed SYNGAP1 loss-of-function mutations or families willing to donate cells for iPSC generation and research.
Not a fit: People whose autism is not caused by SYNGAP1 mutations or those seeking an immediate clinical therapy are unlikely to directly benefit from this preclinical work.
Why it matters
Potential benefit: If successful, this could restore SYNGAP1 protein and open a path toward treatments that address the underlying genetic cause of SYNGAP1-related disorders.
How similar studies have performed: Splice-switching oligonucleotides have been effective in other genetic disorders (for example spinal muscular atrophy) and show preclinical promise, but applying SSOs to SYNGAP1 is a novel approach.
Where this research is happening
Chicago, United States
- University of Chicago — Chicago, United States (Active)
Researchers
- Principal investigator: Zhang, Xiaochang — University of Chicago
- Study coordinator: Zhang, Xiaochang
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.