Phase 12 Study of CRISPR-Cas9 Gene-Edited Donor Kidneys to Reduce Rejection Risk in Adults Undergoing Kidney Transplantation

What this Trial Is About

Researchers are evaluating a new approach to kidney transplantation in adults with end-stage renal disease ESRD using donor kidneys genetically modified with CRISPR-Cas9 to reduce immune rejection. This trial focuses on disrupting key donor human leukocyte antigen HLA genes, including HLA-A, HLA-B, and CIITA, to lower the risk of graft rejection by making the kidney less recognizable to the recipients immune system. The study aims to assess the safety and feasibility of this novel gene-editing method along with its impact on immune responses and graft function over one year after transplant. The trial involves transplanting donor kidneys edited ex vivo with CRISPR-Cas9 to knock out HLA class I heavy chains HLA-A and HLA-B and disable HLA class II expression through CIITA gene disruption. The gene-edited kidney is transplanted using standard surgical techniques, and participants receive usual immunosuppressive medications, which may be adjusted based on the edited kidneys lower immunogenicity. This is a single-arm study where about 90 adult participants will receive the experimental gene-edited kidney graft. Participants will be hospitalized for the transplant surgery and closely monitored afterward with frequent clinic visits. Assessments include tracking serious adverse events, graft survival at six months, acute rejection episodes, donor-specific antibody development, kidney function measured by eGFR, and immune cell responses over 12 months. Safety monitoring will also include checking for any off-target effects of gene editing and long-term transplant outcomes. Participants are followed for at least one year post-transplant to evaluate treatment effects and feasibility.

CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk