<div>Lipid nanoparticles for targeted siRNA delivery &ndash; going from bench to bedside</div>

Abstract

This review covers the basic aspects of small interfering RNA delivery by lipid nano-particles (LNPs) and elaborates on the current status of clinical trials for these systems. We briefly describe the roles of all LNP components and possible strategies for their improvement. We also focus on the current clinical trials using LNP-formulated RNA and the possible outcomes for therapy in the near future. Also, we present a critical analysis of selected clinical trials that reveals the common logic behind target selection. We address this review to a wide audience, especially to medical doctors who are interested in the application of RNA interference–based treatment platforms. We anticipate that this review may spark interest in this particular audience and generate new ideas in target selection for the disorders they are dealing with.

Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming Intracellular Barriers

“…In extracellular space these carriers have neutral charge that provide long circulation times and higher tumor uptake, while in endosomes of cancer cells they acquire positive charge facilitating release of genetic cargo. Thus, the mentioned advantageous properties of LNPs resulted in their early clinical translation ( Zatsepin et al, 2016 ), although the efficacy of endosomal escape for such LNPs ( Gilleron et al, 2013 ), as well as cellular uptake ( Sahay et al, 2013 ), are not very high and require additional optimization.…”

Pulmonary Administration: Strengthening the Value of Therapeutic Proximity

“…siRNA-nanocarriers engineered to tune selectivity of advanced nanoDDS liposomes, polymeric nanoparticles, micelles, solid lipid nanoparticles and inorganic nanoparticles could be designed in order to promote higher bioavailability, stability and residency times at the lung (65)(66)(67). For this reason, inhaled siRNA-based therapy deserves to be explored.…”

Polymers in the Delivery of siRNA for the Treatment of Virus Infections

“…11). These studies have been comprehensively reviewed [21,87,89,101]. During the 2014-2015 Ebola outbreak, for example, clinical trials were conducted for an anti-Ebola siRNA-lipid-bound small interfering RNA (siRNA) known as TKM-130803 [102].…”

“…Retroviruses have the ability to integrate into the host genome, allowing continuous expression of the RNAi treatment, whilst adenoviruses do not. Viral vectors have given significant hope to the longlasting treatment of HIV and hepatitis B and C [62,89,92]. Clinical trials of siRNA delivery using viral vectors have been conducted in HIV patients, in which participants underwent transplantation of lentiviral-transformed haematopoietic progenitor cells designed to express three anti-HIV siRNAs.…”