Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

Abstract

Access to the full text of the published version may require a subscription. Rights AbstractGene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate delivery systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.3 Introduction:

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

“…14 The potential of CDs as delivery agents for therapeutic oligonucleotides is well established. 15,16 Chemical modification of CDs has yielded monodisperse nonviral gene delivery vectors.…”

Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

“…Preventing siRNA digestion by serum nucleases is a key feature for non-viral delivery vectors, particularly in the context of future in vivo usage (Guo et al, 2010).…”

Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells

“…Unlike cationic NPs, which bind to negatively charged cell surfaces, the negatively charged AuNPs-PEG-Tf (~ -43 mV) are unlikely to undergo nonspecific cell uptake. In contrast, the uptake of these Tf-targeted NPs is most probably via receptor-specific uptake [39].…”