Detecting unintended DNA edits from gene therapies
OFF-TARGET RESOURCE CORE
['FUNDING_OTHER'] · CHILDREN'S HOSP OF PHILADELPHIA · NIH-11145245
This project builds ways to find and understand unintended DNA changes caused by AAV gene-editing approaches for people with PKU, hereditary tyrosinemia type 1, or mucopolysaccharidosis type I.
Quick facts
| Phase | ['FUNDING_OTHER'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | CHILDREN'S HOSP OF PHILADELPHIA (nih funded) |
| Locations | 1 site (PHILADELPHIA, UNITED STATES) |
| Trial ID | NIH-11145245 on ClinicalTrials.gov |
What this research studies
This core develops and runs lab tests to find unintended DNA edits that can happen when AAV-based gene-editing treatments are used for conditions like PKU, hereditary tyrosinemia type 1, and MPS I. Researchers will use advanced DNA sequencing, cellular and animal models, and analyses that take human genetic differences into account to map where edits occur and how often. The team will look for large problems such as chromosomal rearrangements, big insertions or deletions, and study whether any off-target edits change how cells behave. Results will support preclinical safety testing and help prepare regulatory (IND) submissions so future clinical trials can be safer.
Who could benefit from this research
Good fit: Ideal candidates are people with phenylketonuria, hereditary tyrosinemia type 1, or mucopolysaccharidosis type I who are considering or eligible for AAV-based gene-editing approaches, or individuals able to donate biological samples for preclinical testing.
Not a fit: People without these genetic disorders or those seeking immediate treatment are unlikely to get direct clinical benefit from this primarily preclinical core.
Why it matters
Potential benefit: If successful, this work could make AAV gene-editing therapies safer by finding harmful unintended edits before human trials.
How similar studies have performed: Related sequencing and off-target detection methods are already used to improve gene-therapy safety, though combining comprehensive off-target, genomic-integrity, and biological-consequence testing across multiple therapy leads is relatively new.
Where this research is happening
PHILADELPHIA, UNITED STATES
- CHILDREN'S HOSP OF PHILADELPHIA — PHILADELPHIA, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: WANG, XIAO — CHILDREN'S HOSP OF PHILADELPHIA
- Study coordinator: WANG, XIAO
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.