Start Date
April 2026
Location
3rd floor - Library
Abstract
Graft rejection remains a major barrier to long-term success in pediatric organ transplantation. This process is driven by the recipient’s immune recognition of non-self major histocompatibility complex (MHC) class I and II antigens expressed on donor tissues, leading to activation of alloreactive cytotoxic T lymphocytes. Current clinical management relies on long-term immunosuppressive therapy to prevent rejection; however, these treatments increase the risk of infection and malignancy, highlighting the need for safer and more targeted approaches.
Recent advances in nanotechnology offer a promising strategy to reduce graft immunogenicity before transplantation. Nanoparticles can be used as a pre-treatment to deliver targeted therapies directly to donor organs during ex vivo preparation, such as normothermic machine perfusion. These nanoparticles can be engineered to selectively downregulate or block MHC expression using CRISPR-Cas9 technology. By modifying the donor organ before implantation, this approach aims to reduce immune activation upon transplantation.
The development of nanoparticle-based preconditioning strategies has the potential to generate immunologically “silent” organs, minimizing or eliminating the need for lifelong systemic immunosuppression. Such innovations could significantly improve transplant outcomes, particularly in pediatric patients, by reducing complications and enhancing long-term graft survival.
Nanoparticle Mediated CRISPRCas9 Deletion of MHC Complex for Mitigating Graft Rejection
3rd floor - Library
Graft rejection remains a major barrier to long-term success in pediatric organ transplantation. This process is driven by the recipient’s immune recognition of non-self major histocompatibility complex (MHC) class I and II antigens expressed on donor tissues, leading to activation of alloreactive cytotoxic T lymphocytes. Current clinical management relies on long-term immunosuppressive therapy to prevent rejection; however, these treatments increase the risk of infection and malignancy, highlighting the need for safer and more targeted approaches.
Recent advances in nanotechnology offer a promising strategy to reduce graft immunogenicity before transplantation. Nanoparticles can be used as a pre-treatment to deliver targeted therapies directly to donor organs during ex vivo preparation, such as normothermic machine perfusion. These nanoparticles can be engineered to selectively downregulate or block MHC expression using CRISPR-Cas9 technology. By modifying the donor organ before implantation, this approach aims to reduce immune activation upon transplantation.
The development of nanoparticle-based preconditioning strategies has the potential to generate immunologically “silent” organs, minimizing or eliminating the need for lifelong systemic immunosuppression. Such innovations could significantly improve transplant outcomes, particularly in pediatric patients, by reducing complications and enhancing long-term graft survival.
