This invention relates to a new siRNA-containing organ storage and reperfusion solution for use in transplantation.

 

Summary of Invention:

This invention relates to a new siRNA-containing organ storage and reperfusion solution for use in transplantation.  The solution comprises siRNA specific to the silencing of genes that contribute to the immunogenicity, survival and/or viability of transplanted tissues, cells or organs. Researchers within the Multi-organ Transplant Program at Lawson have successfully constructed and utilized siRNA to silence the expression of more than 50 immune-associated genes in vitro and in vivo.

Recent studies have focused on genes and combinations of genes that are expressed following ischemia/reperfusion (I/R) injury. I/R injury results from the period of hypoxia prior to and following reperfusion and is one of the primary factors contributing to the immunogenicity and rejection of transplanted organs.

Apoptotic genes (Caspase 3, Caspase 8, Fas), immuno-inflammatory genes (TNFa, RelB) and complement genes (C3, C5aR) have been shown to be significantly expressed on organs subjected to I/R injury. The in vivo silencing of these genes and combinations of these genes with siRNA has been shown to protect against kidney I/R injury and to preserve organ function as measured by serum BUN and creatine levels. Based on the results and similar studies, novel compositions of siRNA-containing organ storage and reperfusion solutions have proposed in order to maintain the viability and decrease the immunogenicity of transplanted tissues, cells or organs.