CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection

Launched by AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLC · Jun 26, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new way to help people who need a liver transplant by using a cutting-edge gene-editing tool called CRISPR. Before the donor liver is transplanted, scientists will edit certain genes to make the liver less likely to be rejected by the patient’s immune system. The goal is to see if this “gene-edited” liver can be safely transplanted and work well, while reducing the chances of the body attacking it after surgery.

Adults aged 16 to 85 who have serious liver disease or liver failure and are waiting for a liver transplant might be able to join the study. To qualify, patients must be medically fit for transplant surgery and able to take standard medications that prevent organ rejection. Participants will receive a donor liver that has had the gene editing done, and they will be closely monitored for safety and how well the liver works over time. This includes regular check-ups and tests to watch the immune response and overall health. Because this is an early study, the main focus is on safety and learning if this new approach is possible for future use.

Gender

ALL

Eligibility criteria

• 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 understand the investigational nature of the trial and provide written informed consent. Patients (and their legal representatives if applicable) must consent to the use of a genetically modified organ and to long-term follow-up including multiple biopsies and immune monitoring.
• • Willingness to comply with all study procedures and availability for the duration of follow-up (including frequent monitoring visits).
• Exclusion Criteria:
• • Active uncontrolled infection (e.g., sepsis, active tuberculosis) that would severely increase transplant risk or confound interpretation of immune-related outcomes.
• • Uncontrolled HIV or chronic viral infections that are not well-managed. (Note: Patients with hepatitis B or C may be included if adequately treated or under control, as these are common in liver failure, but such patients should not have active, replicating virus at transplant if possible.)
• • Multi-organ transplant requirement: Patients needing more than a liver alone (e.g., liver-kidney dual transplant) are excluded, as the trial is only evaluating single organ (liver) outcomes.
• • Pregnancy or breastfeeding: Female participants of childbearing potential must have a negative pregnancy test prior to transplant and must agree to use effective contraception. The effects of a gene-edited organ transplant on a fetus/infant are unknown, and immunosuppressive drugs can also harm a pregnancy.
• • Severe concurrent illness not related to liver disease that would limit survival to \<1 year or make the patient an unsuitable candidate (e.g., advanced heart failure, uncontrolled diabetes with complications, etc.).
• • Allergy or hypersensitivity to study-related products: If any components used in the ex vivo gene editing (such as a specific vehicle or enzyme) have known severe allergies in the recipient, they will be excluded. (For instance, although unlikely, if a patient had a documented severe immune reaction to Streptococcus pyogenes Cas9 or similar proteins, they would not be enrolled.)
• • Inability to follow the protocol or comply with follow-up: this includes psychiatric, social or logistical factors that would prevent adhering to the intense monitoring schedule (for example, lack of reliable transportation or support).