CRISPR-edited donor kidney transplant to reduce rejection risk

Phase 1/2, Single-Arm, Open-Label Trial to Evaluate the Safety, Feasibility, and Immunogenicity of Ex Vivo CRISPR-Cas9 Gene-Edited Donor Kidneys (Knockout of HLA-A, HLA-B, and CIITA) in Human Renal Transplant Recipients

This trial will see if donor kidneys edited with CRISPR to turn off key HLA genes can lower rejection in adults with end-stage kidney disease receiving transplants.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 16 Years to 85 Years
• Sex: All
• Sponsor: American Organ Transplant and Cancer Research Institute LLC (Academic / other)
• Locations: 1 site (Beijing, Changping)
• Trial ID: NCT07053462 on ClinicalTrials.gov

What this trial studies

This phase 1/2 interventional program transplants deceased-donor kidneys that are edited ex vivo with CRISPR‑Cas9 to disrupt HLA‑A, HLA‑B, and CIITA to reduce class I and class II antigen expression. Approximately 90 adult patients with end-stage renal disease who are eligible for kidney transplantation will receive allocated, ABO‑compatible edited kidneys and receive standard perioperative care and immunosuppression. The primary focus is on safety and feasibility of the ex vivo editing and transplant workflow, with secondary measures tracking immune responses, graft function, and operational practicality. While preclinical animal and cell studies support the concept, human transplantation of gene-edited solid organs remains experimental and will be carefully monitored.

Who should consider this trial

Good fit: Adults aged 16–85 with end-stage renal disease who are listed for kidney transplant, medically fit for surgery, and able to receive an allocated, ABO‑compatible deceased donor kidney are ideal candidates.

Not a fit: Patients who are not transplant candidates, lack access to a suitable allocated donor kidney for ex vivo editing, have contraindications to surgery or immunosuppression, or have uncontrolled active infection are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could lower immune-mediated rejection of donor kidneys, potentially reducing long-term immunosuppression needs and prolonging graft survival.

How similar studies have performed: Preclinical animal and cellular studies have shown that removing major HLA molecules can reduce allorecognition, but human use of ex vivo CRISPR‑edited solid organs is largely novel with limited clinical precedent.

Eligibility criteria

Inclusion Criteria:

* Adult patients, age 16 to 85 years, with end-stage renal disease (ESRD) who are candidates for kidney transplantation. This includes patients on dialysis or approaching dialysis who have been evaluated and listed for transplant.
* Eligible for transplant surgery based on medical assessment (i.e., no contraindications to major surgery and transplantation). The patient's overall health status must be sufficient to undergo the transplant procedure and the required immunosuppression.
* Suitable donor organ available: A deceased-donor kidney that meets standard acceptable criteria for transplant (e.g., adequate organ function and anatomy) and is ABO blood type compatible with the recipient. The donor kidney must be allocated to the trial and available for ex vivo gene editing prior to transplantation.
* Informed consent: The patient (or legally authorized representative) is able to understand the experimental nature of the study and has voluntarily signed the informed consent form. The patient must be willing to comply with all study procedures, follow-up visits, and laboratory tests.
* Negative crossmatch (if applicable): No pre-existing anti-donor reactivity that would cause immediate graft failure. (All recipients should have a negative T and B cell crossmatch with the donor organ prior to transplant, as per standard practice, to ensure no strong baseline donor-specific antibodies, especially against any remaining donor HLA such as HLA-C.)
* Women of childbearing potential must have a negative pregnancy test and must agree to use effective contraception during the study and for a period after (to be specified, e.g., 1 year post-transplant), given the use of immunosuppressants and the unknown effects of gene-edited organ transplantation on pregnancy. Men with partners of childbearing potential should also agree to use contraception.
* High immunologic risk patients are eligible: Patients with high panel reactive antibody (PRA) levels or a history of sensitization (from prior transplants, blood transfusions, or pregnancies) are allowed and even anticipated in this trial, as the intervention is designed to benefit patients with broad HLA sensitization. For instance, patients with calculated PRA \> 80% (who have difficulty finding matched donors) can be included. (Such patients must still meet the crossmatch criterion above - any existing antibodies should not target the antigens remaining on the edited graft.)
* Geographic availability: Patients must be available for long-term follow-up in the study center in China or able to travel for scheduled follow-up visits. They should be willing to remain in proximity to the transplant center for the initial post-operative period as per standard transplant care.

Exclusion Criteria:

* Active infection: Any ongoing severe infection that would contraindicate transplantation or be exacerbated by immunosuppression (e.g., active tuberculosis, untreated Hepatitis B or C, HIV with uncontrolled viremia, etc.). Patients with controlled HIV (on stable antiretroviral therapy with undetectable viral load) may be considered on a case-by-case basis, but active uncontrolled infection is excluded.
* Pregnancy or breastfeeding: Pregnant women are excluded due to the need for immunosuppressive drugs and the unknown risks of the investigational intervention on a fetus. Women who are breastfeeding are also excluded due to potential drug excretion in milk and unknown risks to the infant.
* Multi-organ transplant need: Patients requiring more than one organ transplant simultaneously (e.g., kidney + liver, or kidney + heart) are excluded, as this trial focuses on isolated kidney transplant outcomes. (A history of a prior transplant is not an automatic exclusion if the patient now only needs a kidney, but concurrent multi-organ requirements are excluded.)
* Severe co-morbidities that would significantly increase transplant risk or confound results: for example, uncontrolled cardiovascular disease (e.g., recent myocardial infarction, severe heart failure), uncontrolled diabetes with end-organ damage beyond ESRD, severe liver dysfunction, or other life-threatening illnesses unrelated to kidney failure. Such conditions could make the surgery unsafe or the outcome hard to interpret.
* Contraindications to immunosuppression: Patients with conditions that preclude standard immunosuppressive therapy (for instance, a history of anaphylaxis to tacrolimus or mycophenolate that cannot be managed, or chronic infection that would be fatally worsened by immunosuppression) are excluded. The trial still relies on baseline immunosuppressants, so patients must be able to tolerate them.
* Inability to follow the protocol: Patients with significant psychiatric disorders, cognitive impairment, or social situations that would make adherence to the study protocol and follow-up unlikely. This includes inability to give informed consent or lack of support for the intensive follow-up (for example, if the patient is incarcerated or has no fixed address, etc.).
* Prior gene therapy or organ experiment participation: Patients who have previously received any investigational gene therapy, or who have a donor-specific tolerance induction or other experimental transplant treatments ongoing, may be excluded to avoid confounding effects. (This is a precaution to attribute outcomes specifically to the CRISPR-edited organ intervention.)
* Laboratory abnormalities: Any clinically significant abnormalities in baseline labs that would pose added risk - for instance, severe leukopenia or thrombocytopenia that could worsen with immunosuppression, or uncontrolled coagulopathy that raises surgical risk.
* Donor-related exclusions: If the donor kidney, upon retrieval, is found unsuitable for gene editing or transplant (e.g., poor organ quality, unexpected disease in the organ, or if the CRISPR editing fails to achieve sufficient knockout of target genes), the transplant to that patient will not proceed under the study (the patient may either receive a standard transplant off-study or wait for another opportunity). In such a case, the patient might be withdrawn or deferred, but this is a procedural consideration rather than a characteristic of the patient.

Where this trial is running

Beijing, Changping

• Peking University Health Science Center (PKUHSC) — Beijing, Changping, China (Recruiting)

Study contacts

• Study coordinator: Andrew R Linehan

Conditions End-Stage Renal Disease; End Stage Renal Disease on Dialysis; End Stage Renal Disease With Renal Transplant; Kidney Transplant Rejection; Kidney Tumor; Kidney Failure; Kidney Ischemia; HLA Mismatch Immunogenicity