Gene Silencing using siRNA for Preventing Liver Ischaemia-Reperfusion Injury

BACKGROUND: Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation, involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of IRI is a promising therapeutic approach.

OBJECTIVE: This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation.

METHOD: We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs.

RESULTS: We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding siRNA off-target effects.

CONCLUSION: siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what molecules to target and by using more efficient delivery strategies.