siRNA Delivery to the lung: What's new?

Abstract

RNA interference (RNAi) has been thought of as the general answer to many unmet medical needs. After the first success stories, it soon became obvious that short interfering RNA (siRNA) is not suitable for systemic administration due to its poor pharmacokinetics. Therefore local administration routes have been adopted for more successful in vivo RNAi. This paper reviews nucleic acid modifications, nanocarrier chemistry, animal models used in successful pulmonary siRNA delivery, as well as clinical translation approaches. We summarize what has been published recently and conclude with the potential problems that may still hamper the efficient clinical application of RNAi in the lung.

Going beyond the liver: Progress and challenges of targeted delivery of siRNA therapeutics

“…Despite a large number of studies reporting the successful use of siRNA in preclinical models, no clinical translation has yet emerged [78]. For intranasal, intratracheal or inhalation delivery systems, lipids (neutral and cationic), polymers (polyethyleneimine (PEI), poly(lacticco-glycolic acid) (PLGA) etc.…”

Upconversion luminescence tracking of gene delivery via multifunctional nanocapsules

“…Up to now, various types of siRNA-carrier complexes have been explored for effective gene delivery and therapy and could be categorized into two types: viral and non-viral vectors. (Brown et al 2013;Merkel et al 2014;Rychak,Klibanov 2014) Serious immunological problems that might bring about by viral-based vectors greatly limited their applications in clinical therapy, (Everts et al 2006) while non-viral delivery systems, which are typically based on cationic lipids or polymers, have shown great potentials in terms of their simplicity of surface modification and less induction of immune responses. fluorescent or not able to express fluorescent proteins, traditional fluorescent dyes, (Medarova et al 2007) gold nanostructures, (Wu et al 2010) and luminescent QDs Zhang et al 2012) have been employed for construction of multifunctional luminescent nanocarriers.…”

Review of Methods to Study Gene Expression Regulation Applied to Asthma

“…The nucleic acid siRNA can be subjected to chemical modifi cations of the sugar, backbone, or the bases of ribonucleotides in order to avoid nucleases [ 100 ]. Instead of nucleic acid modifi cation, naked siRNA should be delivered with a nanocarrier.…”