Induction of therapeutic gene silencing in leukocyte-implicated diseases by targeted and stabilized nanoparticles: A mini-review

RNA interference (RNAi) is a highly conserved endogenous mechanism that uses small RNA species to guide the sequence-specific silencing of gene expression. The discovery that RNAi functions in mammalian cells to regulate important cellular processes suggested that harnessing these endogenous gene-silencing pathways can prove to be an effective method for the targeted silencing of gene expression. Yet, the key challenge in translating the discovery of RNAi into a novel therapeutic modality is the lack of effective and safe delivery strategies. Here, we describe the major systemic delivery platforms that have been developed. Focus is given to the development of new strategies to target leukocytes, which are among the most difficult cells to transduce with RNAi. Finally, we discuss our strategies to target subsets of leukocytes using integrin-targeted and stabilized nanoparticles (I-tsNPs).

Integrin targeted and stabilized nanoparticles (labeled with Alexa 488) deliver siRNAs (Cy3) into primary leukocytes. This strategy was useful in identifying new drug targets in IBD, prevention of HIV infection and for therapeutic gene silencing.Figure optionsDownload high-quality image (424 K)Download as PowerPoint slide