RecruitingPhase 1Phase 2NCT07053488

CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection

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.

Sponsor

AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLC

Enrollment

90 participants

Start Date

Jun 1, 2025

Study Type

INTERVENTIONAL

Conditions

Liver Cancer Liver Metastases Liver Cirrhosis Liver Diseases Liver Failure Liver Transplant Rejection Liver Steatoses

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.

Eligibility

Min Age: 16 YearsMax Age: 85 Years

Plain Language Summary

Simplified for easier understanding

This pioneering trial tests livers from donors whose immune markers (HLA antigens) have been genetically edited using CRISPR technology. By removing certain immune triggers from the donor organ, researchers hope to reduce the risk of rejection and allow transplant recipients to need less anti-rejection medication. **You may be eligible if...** - You have liver failure and are being evaluated for a liver transplant - You are willing to receive a liver from a CRISPR-edited donor - You meet the standard health and medical requirements for liver transplantation - You are 18 or older **You may NOT be eligible if...** - You have conditions that make liver transplantation too high-risk - You have active cancer or serious infections - You are unable to take anti-rejection medications after transplant - You are pregnant Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALEx Vivo CRISPR-Cas9 Gene Editing of Donor Liver

Donor liver tissue is perfused outside the body with a CRISPR-Cas9 RNP complex targeting HLA-A, HLA-B, and CIITA, to create a hypoimmunogenic graft. After confirming successful gene knockout, the liver is transplanted into the patient following standard surgical techniques. Post-operative care includes routine immunosuppressive therapy with planned adjustments based on the patient's tolerance and evidence of graft immunogenicity.