Clinical trial · Interventional
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.
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (7)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Liver Cancer | Malignant Liver Neoplasm | CURATED_EXACT | 0.92 |
| Liver Cirrhosis | — | UNRESOLVED | — |
| Liver Diseases | — | UNRESOLVED | — |
| Liver Failure | — | UNRESOLVED | — |
| Liver Metastases | — | UNRESOLVED | — |
| Liver Steatoses | — | UNRESOLVED | — |
| Liver Transplant Rejection | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Ex Vivo CRISPR-Cas9 Gene Editing of Donor Liver | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- CRISPR-Edited Donor Liver Transplant
- description
- Participants undergo orthotopic liver transplantation using a donor liver that has been ex vivo gene-edited by CRISPR-Cas9 to knock out HLA class I (A, B) and class II (via CIITA) genes. There is no comparator arm; outcomes will be compared to historical norms of unedited transplants for context.
- interventionNames
- Biological: Ex Vivo CRISPR-Cas9 Gene Editing of Donor Liver
Primary outcomes (3)
- measure
- Incidence of Grade ≥3 Treatment-Emergent Adverse Events (TEAEs)
- timeFrame
- Day 1 to Day 90
- description
- Number of participants experiencing ≥1 CTCAE v5.0 Grade 3-5 TEAE judged related to the gene-edited liver transplant procedure
- measure
- Feasibility of Ex Vivo HLA Gene Editing
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 16 Years
- Maximum age
- 85 Years
Show eligibility criteria text
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).
References
Publications (0)
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