A Phase 1/2, Open-Label, Single-Arm Study to Evaluate the Safety, Immunogenicity Reduction, Transplant Function, and Feasibility of Ex Vivo CRISPR-Cas9 Gene-Edited Donor Liver Transplantation Targeting HLA Class I (HLA-A, HLA-B) and Class II (Via CIITA) Genes.

What this Trial Is About

Researchers are evaluating the use of ex vivo CRISPR-Cas9 genome editing on donor liver grafts to reduce immune rejection in patients with end-stage liver disease or acute liver failure. The study aims to create a "hypoimmunogenic" liver by knocking out HLA-A and HLA-B genes and disabling HLA class II expression through targeting the CIITA gene. This trial focuses on assessing the safety, feasibility, and immune response reduction of CRISPR-edited livers transplanted into patients. In this trial, deceased-donor livers undergo gene editing outside the body during machine perfusion using a CRISPR-Cas9 complex targeting HLA-A, HLA-B, and CIITA genes. The edited liver, confirmed for successful gene knockout, is then transplanted using standard surgical methods. Participants receive routine immunosuppressive therapy after surgery, with planned adjustments based on their response and graft immunogenicity. The study does not include a comparator group but compares outcomes to historical data of unedited liver transplants. Participants will be monitored closely with frequent visits to assess safety, graft function, immune response, and transplant rejection over time. Primary outcomes include adverse events, gene editing feasibility, and graft failure within 90 days. Secondary measures evaluate acute rejection, immune markers, graft survival, patient survival, immunosuppression reduction, and off-target effects up to 24 months. Long-term follow-up includes biopsies and immune monitoring, and participants are expected to comply with study procedures throughout the observation period.

CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection