Human liver cell models to improve gene therapy for hemophilia A

Human Hepatocyte and Discovery Core

NIH-funded research Indiana University Indianapolis · NIH-11325356

Using human liver cells and humanized mouse models to find why AAV gene therapy for hemophilia A can lose effect or harm the liver, with the aim of making treatments last longer and safer for people with hemophilia A.

Quick facts

Grant typeP01 program project
Study typeNIH-funded research
Funding institutionIndiana University Indianapolis NIH-funded
Lab location1 site (Indianapolis, United States)
Project IDNIH-11325356 on NIH RePORTER

What this research studies

Researchers will use three human-based liver models to study AAV-delivered FVIII gene therapy from a patient's point of view. The team will grow primary human hepatocytes in lab dishes that keep liver cells working, use mice whose livers are largely repopulated with human hepatocytes for in-body testing, and use mice that also carry human immune cells to study immune reactions. They will look specifically at how the AAV vectors interact with human liver cells, how FVIII expression changes over time, and what causes liver injury or loss of benefit. The aim is to inform safer, longer-lasting gene therapy approaches for people living with hemophilia A.

Who could benefit from this research

Good fit: Ideal participants would be people with hemophilia A—particularly those interested in or considering AAV gene therapy—or individuals who can donate liver tissue or blood cells for research.

Not a fit: People with bleeding disorders not caused by factor VIII deficiency or those who are not candidates for liver-directed treatments are unlikely to benefit directly from this work.

Why it matters

Potential benefit: Could lead to AAV gene therapies for hemophilia A that work for longer and have fewer liver or immune-related side effects.

How similar studies have performed: Previous AAV gene therapy trials for hemophilia A have shown initial increases in FVIII but often declining levels and some liver toxicity, so this project builds on existing work to address those persistent problems.

Where this research is happening

Indianapolis, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.