Knocking down barriers: advances in siRNA delivery

By Kathryn A. Whitehead, Robert Langer, Daniel G. Anderson. Nature reviews. Drug discovery, 2009

2,795 citations recorded by the source corpus.

In the 10 years that have passed since the Nobel prize-winning discovery of RNA interference (RNAi), billions of dollars have been invested in the therapeutic application of gene silencing in humans. Today, there are promising data from ongoing clinical trials for the treatment of age-related macular degeneration and respiratory syncytial virus. Despite these early successes, however, the widespread use of RNAi therapeutics for disease prevention and treatment requires the development of clinically suitable, safe and effective drug delivery vehicles. Here, we provide an update on the progress of RNAi therapeutics and highlight novel synthetic materials for the encapsulation and intracellular delivery of nucleic acids.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b368b90f3ff6d9a8ac273e05c8e8ff505a11ad44

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Citations in the corpus

Interactions of nanomaterials and biological systems: implications to personalized nanomedicine (2012, background): “In these systems, membrane-disruptive properties can be obtained by using proteins and peptides [143, 144], polymers [145, 146] or simply by incorporating a high number of ionisable amine groups to exploit the proton sponge effect [117].”
Innovative approaches for cancer treatment: current perspectives and new challenges (2019, background): “Consequently, different delivery strategies are currently under study, such as chemical modification, encapsulation into lipid or polymeric carriers or conjugation with organic molecules (polymers, peptides, lipids, antibodies, small molecules [181], for efficient targeting [182, 183]).”
Delivery of siRNA Therapeutics: Barriers and Carriers (2010, background): “After entering the cell, siRNA must escape from the endosomes and be released from its carrier to the cytosol in order to be loaded onto RISC ( 24 ).”
Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “Nanoparticles offer the possibility to encapsulate poorly soluble drugs [8, 9], protect therapeutic molecules [10], and modify their blood circulation and tissue distribution profiles [11, 12].”
Smart nanoparticles for cancer therapy (2023, background): “313 The success of nucleic acid drugs largely bene ﬁ ts from the development of drug delivery system using smart nanoparticles.”
Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling (2013, positive): “Overall, C12-200-based cationic LNPs utilize macropinocytosis to enter cells and bypass the early endosomes; a small fraction is directed to the ERC while most LNPs traffic towards the late endosome from where they are routed to the lysosomes.”
Principles of early drug discovery (2011, background): “However, RNAi technology still has the major problem of delivery to the target cell, but many viral and non-viral delivery systems are currently under investigation (for review see Whitehead et al., 2009).”
Non‐coding RNAs: regulators of disease (2010, background): “Nonetheless, multiple modes of administration have been developed, including viral, liposome and nanoparticle delivery systems, and there are currently multiple ongoing clinical trials targeting age-related macular degeneration, respiratory syncytial virus, acute renal failure, hepatocellular carcin”
Rational design of cationic lipids for siRNA delivery (2010, methodology): “To date, formulation in lipid nanoparticles (LNPs) represents one of the most widely used strategies for in vivo delivery of siRN”
Subcellular targeting strategies for drug design and delivery (2010, background): “Such prodrugs could be used to evade lysosomal degradation and to increase the efficiency of cytosolic release of molecules such as siRNA”