Overcoming RNAi transduction in leukocytes using targeted and stabilized nanoparticles

RNAi-based approaches have contributed significantly to the improved understanding of gene expression and function in vitro. The ability to apply these strategies in vivo to validate the role of specific genes in normal or pathological conditions, and to induce gene silencing, has led to new possibilities for using RNAi as a novel therapeutic modality. However, the translation of RNAi from an effective genomic tool into clinical applications has been hindered by the challenge of delivering RNAi molecules to their target tissues by systemic administration, particularly to hematopoietic cells. This feature review describes the current systemic RNAi delivery platforms targeted to leukocytes, with a focus on the integrin-targeted stabilized nanoparticles strategy, which uses leukocyte integrins for the delivery of siRNAs exclusively to cells of the immune system.