Therapeutic alteration of transplantable tissues through
The present invention, at least in part, relates to the discovery of efficacious delivery of an RNAi agent (in preferred aspects of the invention, an siRNA) to a transplantable tissue. Organ rejection, transplantation-mediated transmission of viral infection, and triggering of apoptosis in transplanted tissues can each be minimized by the methods and compositions of the instant invention. The RNAi agent(s) of the instant invention can be delivered as “naked” molecules, or using liposomal and other modes of delivery, to transplantable tissues. Such delivery can occur via perfusion of the RNAi agent in solution through the vasculature of a whole or partial organ; or tissues including transplantable cells and cell lines may be bathed, injected or otherwise treated with RNAi agents. Preferred transplantable tissues include, for example, pancreas, liver, kidney, heart, lung, and all cells and cell lines derived from such tissues (e.g., pancreatic islet cells that may, e.g., be transplanted as a treated population).
1. A method of inhibiting apoptosis-induced ischemic injury of a transplanted allograft kidney, comprising perfusing the vasculature of the allograft kidney, before and during procurement, with an RNAi agent that is sufficiently complementary to p53 RNA to direct RNAi, and reduce the production of p53 within the allograft kidney, thereby causing the allograft kidney to have an overall lower level of p53 relative to an untreated allograft kidney, wherein the method is carried out in the absence of electroporation of the kidney.
2. The method of claim 1 , wherein the RNAi agent is siRNA.
3. The method of claim 1 , wherein the allograft kidney is perfused with a solution containing said RNAi agent by retrograde or anterograde delivery.
4. The method of claim 1 , wherein the perfused RNAi agent contacts the kidney via lipid-mediated delivery or as a component of a liposomal delivery preparation.
5. The method of claim 1 , wherein the RNAi agent is perfused in a preservation solution that additionally comprises either saline or an immunosuppressant.
6. The method of claim 5 , wherein the siRNA is either a single stranded siRNA (ss-siRNA) or a double stranded siRNA (ds-siRNA).