Protein-based vehicles for biomimetic RNAi delivery

Abstract

Broad translational success of RNA interference (RNAi) technology depends on the development of effective delivery approaches. To that end, researchers have developed a variety of strategies, including chemical modification of RNA, viral and non-viral transfection approaches, and incorporation with delivery vehicles such as polymer- and lipid-based nanoparticles, engineered and native proteins, extracellular vesicles (EVs), and others. Among these, EVs and protein-based vehicles stand out as biomimetically-inspired approaches, as both proteins (e.g. Apolipoprotein A-1, Argonaute 2, and Arc) and EVs mediate intercellular RNA transfer physiologically. Proteins specifically offer significant therapeutic potential due to their biophysical and biochemical properties as well as their ability to facilitate and tolerate manipulation; these characteristics have made proteins highly successful translational therapeutic molecules in the last two decades. This review covers engineered protein vehicles for RNAi delivery along with what is currently known about naturally-occurring extracellular RNA carriers towards uncovering design rules that will inform future engineering of protein-based vehicles.

RNA Interference: A Novel Technology for Virus Disease Management in Crop Plants

“…RNAi can promote the screening and production of drugs by discovering genes that can impart drug resistance or genes whose mutantphenotypes area meliorated by drug therapy, providing information on modes of action of new compounds.Itwas also a preferred method of application to investigate the concurrent functions of multiple genes expressing the functions in organisms, where duplication occurs concerning a specific function, as many of these genes may be silenced simultaneously. The polymer and lipidnanoparticles-based delivery of siRNA was effective in delivering the siRNA into the human body that facilitates the broad translational success of RNA interference (RNAi) technology in therapeutic applications (Pottash et al, 2019).…”

The nanostructured secretome

“…The use of both bare and coated nanosized macromolecular complexes for targeted drug delivery purposes is largely reported. 17,[123][124][125] Circulating proteins are highly uptaken by cancer cells through the overexpression of specific surface receptors. Therefore, globular transport proteins often result in biological NPs with intrinsic tumor-targeting abilities.…”

“…127 Ago proteins are largely known to bind and mediate the intercellular transfer of hydrophobic and poorly stable non-coding genetic material, specifically silencing RNAs (siRNAs) and miRNAs. 125 siRNAs regulate cell metabolism through gene silencing and recently emerged as novel therapeutic strategy for a broad range of life-threatening pathologies. However, siRNA application is severely hampered by their poor stability.…”

Reconfiguring Nature’s Cholesterol Accepting Lipoproteins as Nanoparticle Platforms for Transport and Delivery of Therapeutic and Imaging Agents

“…This platform was adapted also for the delivery of anti-vascular endothelial growth factor receptor 2 (VEGFR2) oligonucleotides to suppress angiogenesis [200], to knockdown VEGFR expression in human umbilical vein endothelial cells and to promote cell survival. Overall for gene-based therapy with siRNA and other nucleic acids such as adenoviral DNA [201] delivery via the HDL platform holds promise and potential [202] especially for cancer treatment. Further optimization is needed with focus on targeting capability, decreasing enzymatic degradation and identifying effective endosomal/lysosomal escape, dosage and half-life.…”