CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk

Summary

This clinical trial investigates the transplantation of donor kidneys that have been genetically modified ex vivo using CRISPR-Cas9 genome editing to reduce immunogenicity and transplant rejection. Donor kidney grafts will have key human leukocyte antigen (HLA) genes disrupted - specifically, knockout of HLA class I heavy chains HLA-A and HLA-B, along with disabling HLA class II expression by targeting the CIITA gene (a master regulator of HLA-DR/DQ/DP). Approximately 90 adult end-stage renal disease patients will receive a CRISPR-edited donor kidney transplant. The primary objectives are to assess the safety and feasibility of this novel intervention, while secondary objectives evaluate the reduction in immune responses (immunogenicity), graft function, and the practicality of implementing ex vivo gene-edited organ transplantation in humans. By knocking out major donor HLA molecules, the trial aims to reduce T-cell and antibody-mediated recognition of the graft, potentially lowering rejection rates and reliance on high-dose immunosuppressants. Safety, including any off-target effects or unanticipated immune reactions, will be closely monitored, and transplant outcomes will be tracked for one year post-transplant.

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

Interventions

BIOLOGICAL

Ex Vivo CRISPR-Cas9 Gene Editing of Donor Kidney

The donor kidney is treated outside the body with CRISPR-Cas9 ribonucleoprotein complexes targeting the genes HLA-A, HLA-B, and CIITA. This genetic intervention knocks out HLA-A/B on donor cells and disables expression of HLA-DR, -DQ, -DP by disrupting CIITA (essential for class II antigen presentation). The goal is to create a transplanted organ with greatly reduced immunogenic surface proteins. (This is a one-time genetic manipulation applied to the donor organ prior to transplantation; no direct gene therapy is given to the patient's own cells.)

PROCEDURE

Kidney Transplantation with Standard Care

After gene editing, the donor kidney is implanted into the recipient in a surgical transplant procedure. Standard peri-operative care is provided. All patients will receive standard immunosuppressive therapy post-transplant (such as tacrolimus, mycophenolate, and prednisone, per center protocol) to prevent rejection, though the regimen may be tailored based on the edited graft's expected lower immunogenicity. Patients will be hospitalized for transplant and monitored closely during the immediate post-op period, then followed in clinic frequently for transplant aftercare.

Sponsors & Collaborators

• AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLC

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

16 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-01

Primary Completion

2027-12-18

Completion

2028-12-28

Countries

• China

Study Locations