Why AAV gene therapy gets turned off in human liver cells
Dissecting AAV silencing in humanized mice
['FUNDING_R01'] · DUKE UNIVERSITY · NIH-11258501
This project looks for ways to stop AAV-based gene treatments from being switched off in human liver cells so people with liver genetic disorders might get longer-lasting benefit.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | DUKE UNIVERSITY (nih funded) |
| Locations | 1 site (DURHAM, UNITED STATES) |
| Trial ID | NIH-11258501 on ClinicalTrials.gov |
What this research studies
Researchers use mice that carry human liver cells so they can watch how AAV-delivered genes behave in real human hepatocytes inside a living body. They will study a cellular silencing system called the Human Silencing Hub (HUSH) to learn how it may turn off AAV transgenes, including experiments using liver cells from patients with methylmalonic acidemia as a proof-of-concept. Finally, the team will test different AAV vector designs and drugs to try to prevent or reverse silencing and restore gene expression.
Who could benefit from this research
Good fit: Ideal candidates would be people with genetic liver disorders (for example methylmalonic acidemia) who can provide liver-derived samples or otherwise collaborate with the research team.
Not a fit: People whose conditions are unrelated to liver-directed gene therapy or who cannot provide samples are unlikely to gain direct benefit from participation.
Why it matters
Potential benefit: If successful, this work could make liver-directed AAV gene therapies work longer and more reliably for people with genetic liver diseases.
How similar studies have performed: AAV liver gene therapies have shown success in some disorders, but transgene silencing is a known hurdle and targeting the HUSH pathway represents a newer, less-tested approach.
Where this research is happening
DURHAM, UNITED STATES
- DUKE UNIVERSITY — DURHAM, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: BISSIG, KARL-DIMITER — DUKE UNIVERSITY
- Study coordinator: BISSIG, KARL-DIMITER
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.
Conditions: Acid Maltase Deficiency Disease