Abstract
The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.
Highlights
Gene therapy is a relatively recent approach in the management of human diseases and has resulted in an increasingly interest as therapeutic strategy
The efforts made to develop RNA interference (RNAi)-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus
Mannosylated SLNs loaded with hepatitis B surface antigen (HBsAg) were subcutaneously administered in vivo in mice and sustained antibody titer was obtained; these results demonstrated the potential of SLNs as carriers for vaccine delivery against HBV [59]
Summary
Gene therapy is a relatively recent approach in the management of human diseases and has resulted in an increasingly interest as therapeutic strategy. Vectors that were developed for DNA delivery are being applied for siRNA delivery In spite of their different physicochemical properties and the need to be transported to different parts of the cell (plasmid DNA needs to be transported into nucleus for gene expression whereas siRNA reaches its target in the cytoplasm), a number of publications describe the use of SLNs for delivery of both DNA [39, 72,73,74] and RNAi mediated molecules [75,76,77,78] with successful results. Cationic lipid-based liposomes are able to complex with negatively charged nucleic acid via electrostatic interactions, resulting in complexes that offer biocompatibility, low toxicity, and the possibility of large-scale production required for in vivo clinical applications [104]. Liposomes have been widely studied as RNAi carriers as potential treatment of viral infections such as HCV, HBV, and VIH, among others [33, 34, 48, 49, 111]
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