Conjugates of small targeting molecules to non-viral vectors for the mediation of siRNA.

UNLABELLED: To use siRNA (small interfering RNA) for gene therapy, a gene delivery system is often necessary to overcome several challenging requirements including rapid excretion, low stability in blood serum, non-specific accumulation in tissues, poor cellular uptake and inefficient intracellular release. Active and/or passive targeting should help the delivery system to reach the desired tissue or cell, to be internalized, and to deliver siRNA to the cytoplasm so that siRNA can inhibit protein synthesis. This review covers conjugates of small targeting molecules and non-viral delivery systems for the mediation of siRNA, with a focus on their transfection properties in order to help the development of new and efficient siRNA delivery systems, as the therapeutic solutions of tomorrow. STATEMENT OF SIGNIFICANCE: The delivery of siRNA into cells or tissues remains to be a challenge for its applications, an alternative strategy for siRNA delivery systems is direct conjugation of non-viral vectors with targeting moieties for cellular delivery. In comparison to macromolecules, small targeting molecules have attracted great attention due to their many potential advantages including significant simplicity and ease of production, good repeatability and biodegradability. This review will focus on the most recent advances in the delivery of siRNA using conjugates of small targeting molecules and non-viral delivery systems. Based the editor's suggestions, we hope the revised manuscript could provide more profound understanding to the conjugates of targeting molecules to vectors for mediation of siRNA.