Liver-directed gene delivery to restore clotting factor in hemophilia B and other inherited liver diseases
Official title: Hepatic gene transfer for the treatment of hemophilia B and other genetic diseases
Funded at Stanford University · NIH-11257294 · Data updated 2026-11-12
This research uses a liver-targeted viral gene delivery approach to help adults with hemophilia B produce the missing clotting protein and could be applied to other inherited liver disorders.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Stanford University NIH-funded |
| Lab location | 1 site (Stanford, United States) |
| Project start | September 1, 2000 |
| Project end | December 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $687,313 |
| NIH project number | 5R01HL064274-24 |
| Project ID | NIH-11257294 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults with hemophilia B or other inherited liver metabolic disorders who meet clinical trial eligibility and are interested in gene-based approaches would be the most relevant candidates.
✕Less likely to help
People with strong pre-existing immunity to AAV, severe liver damage, or very young children whose livers are still growing may not receive benefit from this approach.
What this research studies
Researchers are working with adeno-associated viral (AAV) vectors to insert a therapeutic gene next to the liver's albumin gene so that the liver can make both albumin and the therapeutic protein, such as factor IX. The team is improving a non-cutting (non-nuclease) AAV-homologous recombination method that previously corrected hemophilia B in mice but has low efficiency. They will use cell studies, animal models, and high-throughput sequencing to trace where therapeutic products come from and identify factors that increase correct insertion and reduce off-target integration. The work aims to boost durable protein production early in life and reduce loss of the therapeutic gene during liver growth.
Why it matters
Potential benefit: If successful, this approach could provide longer-lasting production of clotting factor IX from a single liver-directed treatment, reducing bleeding episodes and treatment burden.
How similar studies have gone: AAV liver gene therapies have produced durable factor IX expression in some adult hemophilia B trials and the AAV-homologous recombination approach corrected disease in mouse models, though human efficiency remains limited.
Where this research is happening
-
Stanford University
Stanford, United States Active
Researchers
- Principal investigator: Kay, Mark a — Stanford University
- Study coordinator: Kay, Mark a
Related research
Other NIH-funded projects on the same topics.
-
cGMP production of FVIII-making placental cells to help people with Hemophilia A
A new, patient-friendly therapy aims to make FVIII-producing placental cells in the lab to help adults with Hemophilia A, potentially offering a longer-lasting and more affordable treatment.
-
Enhancing immune regulation in gene therapy for hemophilia (new approaches to safer treatment)
A patient-focused overview of a long-running NIH grant exploring how to make gene therapy for hemophilia safer by teaching the body’s immune system to tolerate the therapeutic protein.
-
A safer, longer-lasting gene delivery approach for Hemophilia A using improved nonviral vectors
Researchers are testing a new type of nonviral gene delivery that could provide longer expression of a therapeutic gene for adults with Hemophilia A.
-
Non-viral gene therapy approach to permanently fix hemophilia B
A new gene therapy approach aims to permanently correct hemophilia B without using viruses, potentially reducing bleeding events for people with this condition.
-
Hemophilia Point-of-Care Test Gets Regulatory Ready
A new point-of-care test for hemophilia A measures FVIII and emicizumab to help doctors manage bleeding risk quickly, with plans to obtain regulatory clearance.
-
Hemophilia A: studying why some people develop inhibitors to FVIII across families
This NIH grant funds a multi-year program to follow families affected by severe hemophilia A to understand why some individuals develop antibodies against factor VIII.
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.