Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion.

ABSTRACT: Organ gene therapy represents a promising tool to correct diseases or improve graft survival after transplantation. Polymorphic variation of the major histocompatibility complex (MHC) antigens remains a major obstacle to long-term graft survival after transplantation. Previously, we demonstrated that MHC-silenced cells are protected against allogeneic immune responses. We also showed the feasibility to silence MHC in the lung. Here, we aimed at the genetic engineering of the kidney toward permanent silencing of MHC antigens in a rat model. We constructed a sub-normothermic ex vivo perfusion system to deliver lentiviral vectors encoding shRNAs targeting β2-microglobulin and the class II transactivator to the kidney. In addition, the vector contained the sequence for a secreted nanolu

SUBMITTER: Yuzefovych Y 

PROVIDER: S-EPMC7042208 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature