Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

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.

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Its advantages are its biocompatibility, reproducibility, and ease of large-scale production [259]. A number of conventional reagents are currently available, including Lipofectamine ® , siPORT™, HiPerFect, Oligofectamine™, MaxSuppressor™, DharmaFECT ® , SilentFect™, and NeuroPorter™.…”

Vaginal gene therapy

“…Typically, the two most used RNAi molecules are short-interfering RNA (siRNA) and short-hairpin RNA (shRNA) [8]. siRNAs are doublestranded RNA molecules of about 19-23 base pair nucleotides in length, able to mediate site-specific split and destruction of the targeted messenger RNA (mRNA).…”

“…Table 1 shows the indications of the approved, ongoing or completed clinical trials with gene therapy and the number of events related to each worldwide [9]. Indications addressed by gene therapy clinical trials include cancer diseases, monogenic diseases, infectious diseases, neurological diseases, and inflammatory diseases, among others [8]. However, most products under investigation do not reach clinical phases.…”

Novel Prospective Treatment Options

“…On the other hand the action of shRNA is similar to gene therapy, as they get expressed on promoters and cause long term effects. Various viral and non-viral delivery mechanisms and active targeting strategies have been developed to deliver these active agents into the target cells [107,108].…”