CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection
This early-phase clinical trial will assess the use of ex vivo CRISPR-Cas9 genome editing on donor liver grafts to reduce immunogenicity before transplantation. Donor livers will have HLA-A and HLA-B genes knocked out, and HLA class II expression disabled (by targeting the CIITA transactivator gene), aiming to create a
| Condition(s) | Liver Diseases, Liver Cancer, Liver Cirrhosis, Liver Failure, Liver Metastases, Liver Transplant Rejection, Liver Steatoses |
|---|---|
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Study type | Interventional |
| Summary | This early-phase clinical trial will assess the use of ex vivo CRISPR-Cas9 genome editing on donor liver grafts to reduce immunogenicity before transplantation. Donor livers will have HLA-A and HLA-B genes knocked out, and HLA class II expression disabled (by targeting the CIITA transactivator gene), aiming to create a "hypoimmunogenic" organ less prone to rejection. The edited liver is then transplanted into patients with end-stage liver disease. The primary focus is on safety and feasibility - determining whether a CRISPR-edited liver can be transplanted successfully and function normally - as well as evaluating reductions in immune response (acute rejection, anti-donor T cell activation) and graft function over time. |
| Who can participate | Inclusion Criteria: * Adults aged 16-85 (inclusive) with end-stage liver disease or acute liver failure who are eligible for liver transplantation. * Require a liver transplant and have been allocated a donor liver graft (from a deceased donor) that will be used in the study after gene editing. * No immediately available fully HLA-matched donor (since the study targets patients who would otherwise receive an HLA-mismatched organ; standard allocation generally does not consider HLA matching for liver, so most patients will qualify). * Medically suitable for transplant surgery and able to tolerate standard immunosuppressive therapy (no contraindications to transplant such as uncontrolled infection or other active serious disease that would preclude surgery). * Informed Consent: Able to under |
| Ages | 16 Years to 85 Years |
| Sex | All |
| Lead sponsor | AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLC |
| Locations | Beijing, Changping, China |
| Start date | 2025-06-01 |
| NCT ID | NCT07053488 |
| Official listing | https://clinicaltrials.gov/study/NCT07053488 |