Strategies, design, and chemistry in siRNA delivery systems

Y Dong, DJ Siegwart, DG Anderson - Advanced drug delivery reviews, 2019 - Elsevier
Emerging therapeutics that utilize RNA interference (RNAi) have the potential to treat broad
classes of diseases due to their ability to reversibly silence target genes. In August 2018, the …

siRNA versus miRNA as therapeutics for gene silencing

JKW Lam, MYT Chow, Y Zhang, SWS Leung - Molecular Therapy-Nucleic …, 2015 - cell.com
Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs
(miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently …

Enhancing siRNA efficacy in vivo with extended nucleic acid backbones

K Yamada, VN Hariharan, J Caiazzi, R Miller… - Nature …, 2024 - nature.com
Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to
inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS) …

Current development of siRNA bioconjugates: from research to the clinic

IV Chernikov, VV Vlassov… - Frontiers in …, 2019 - frontiersin.org
Small interfering RNAs (siRNAs) acting via RNA interference mechanisms are able to
recognize a homologous mRNA sequence in the cell and induce its degradation. The main …

RNA interference (RNAi)-based therapeutics: delivering on the promise?

ML Bobbin, JJ Rossi - Annual review of pharmacology and …, 2016 - annualreviews.org
A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although
there were initial difficulties in achieving efficacious results with RNAi without toxic side …

Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity

H Zhang, J Vandesompele, K Braeckmans… - Chemical Society …, 2024 - pubs.rsc.org
Gene therapy is on its way to revolutionize the treatment of both inherited and acquired
diseases, by transferring nucleic acids to correct a disease-causing gene in the target cells …

From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization

MK Schlegel, MM Janas, Y Jiang, JD Barry… - Nucleic acids …, 2022 - academic.oup.com
Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target
effects as a major driver of hepatotoxicity for GalNAc–siRNA conjugates. Here, we …

Action and reaction: the biological response to siRNA and its delivery vehicles

RL Kanasty, KA Whitehead, AJ Vegas, DG Anderson - Molecular Therapy, 2012 - cell.com
RNA interference (RNAi)-based therapeutics have significant potential for the treatment of
human disease. Safe and effective delivery of RNA to target tissues remains a major barrier …

Editorial focus: understanding off-target effects as the key to successful RNAi therapy

R Bartoszewski, AF Sikorski - Cellular & molecular biology letters, 2019 - Springer
With the first RNA interference (RNAi) drug (ONPATTRO (patisiran)) on the market, we
witness the RNAi therapy field reaching a critical turning point, when further improvements in …

Locked vs. unlocked nucleic acids (LNA vs. UNA): contrasting structures work towards common therapeutic goals

MA Campbell, J Wengel - Chemical Society Reviews, 2011 - pubs.rsc.org
Oligonucleotide chemistry has been developed greatly over the past three decades, with
many advances in increasing nuclease resistance, enhancing duplex stability and assisting …