RNA interference (RNAi) is an evolutionary conserved highly specific gene-silencing
mechanism initiated by small interfering RNA (siRNA) molecules. Fast-paced preclinical and clinical
studies helped the siRNA technology become an efficient tool for undruggable targets in different diseases
including genetic diseases, viral diseases and cancer. Despite great feature of siRNAs that can
down-regulate any protein in the cells, the full potential and the success of the preclinical studies could
not be translated into largely successful clinical outcomes. It has become clear that the possibility of
overcoming the pitfalls for in vivo siRNA therapy fully depends on delivery systems. In this review, we start with the
challenges and barriers for in vivo siRNA delivery. Then we briefly discuss the recent developments in siRNA modification
technology. We specifically focused on siRNA lipidation and delivery approaches with special emphasis on the lipid
based hybrid systems. Here we summarize the journey of lipid-based micelle-like nanoparticle systems that combine longevity
in blood, effective cellular uptake and endosomal escape for successful siRNA delivery and discuss the multifunctional
stimuli-sensitive systems based on lipids as the next generation smart systems.
Keywords: siRNA, lipid-based delivery, micelle-like nanoparticles, stimuli-sensitive carriers, multifunctional carriers, polyethyleneimine.
Rights & PermissionsPrintExport