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 …

Targeting RNA with synthetic oligonucleotides: clinical success invites new challenges

CR Hofman, DR Corey - Cell chemical biology, 2024 - cell.com
Synthetic antisense oligonucleotides (ASOs) and duplex RNAs (dsRNAs) are an
increasingly successful strategy for drug development. After a slow start, the pace of success …

Shorter Is Better: The α-(l)-Threofuranosyl Nucleic Acid Modification Improves Stability, Potency, Safety, and Ago2 Binding and Mitigates Off-Target Effects of Small …

S Matsuda, S Bala, JY Liao, D Datta… - Journal of the …, 2023 - ACS Publications
Chemical modifications are necessary to ensure the metabolic stability and efficacy of
oligonucleotide-based therapeutics. Here, we describe analyses of the α-(l)-threofuranosyl …

Silencing or stimulation? siRNA delivery and the immune system

KA Whitehead, JE Dahlman, RS Langer… - Annual review of …, 2011 - annualreviews.org
Since its inception more than a decade ago, the field of short interfering RNA (siRNA)
therapeutics has demonstrated potential in the treatment of a wide variety of diseases. The …

Acyclic (S)-glycol nucleic acid (S-GNA) modification of siRNAs improves the safety of RNAi therapeutics while maintaining potency

M Egli, MK Schlegel, M Manoharan - Rna, 2023 - rnajournal.cshlp.org
Glycol nucleic acid (GNA) is an acyclic nucleic acid analog connected via phosphodiester
bonds. Crystal structures of RNA–GNA chimeric duplexes indicated that nucleotides of the …

5′‐(E)‐Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA–GalNAc Conjugates

R Parmar, JLS Willoughby, J Liu, DJ Foster… - …, 2016 - Wiley Online Library
Small interfering RNA (siRNA)‐mediated silencing requires siRNA loading into the RNA‐
induced silencing complex (RISC). Presence of 5′‐phosphate (5′‐P) is reported to be …

Specificity of oligonucleotide gene therapy (OGT) agents

DD Nedorezova, MV Dubovichenko… - …, 2022 - pmc.ncbi.nlm.nih.gov
Oligonucleotide gene therapy (OGT) agents (eg antisense, deoxyribozymes, siRNA and
CRISPR/Cas) are promising therapeutic tools. Despite extensive efforts, only few OGT drugs …

5΄-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo

RA Haraszti, L Roux, AH Coles, AA Turanov… - Nucleic acids …, 2017 - academic.oup.com
Abstract 5΄-Vinylphosphonate modification of siRNAs protects them from phosphatases, and
improves silencing activity. Here, we show that 5΄-vinylphosphonate confers novel …

A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

JB Bramsen, MM Pakula, TB Hansen… - Nucleic acids …, 2010 - academic.oup.com
Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene
function in mammalian cells yet trigger unintended gene silencing due to their inherent …

Mitigating off‐target effects of small RNAs: conventional approaches, network theory and artificial intelligence

Z Bereczki, B Benczik, OM Balogh… - British Journal of …, 2025 - Wiley Online Library
Three types of highly promising small RNA therapeutics, namely, small interfering RNAs
(siRNAs), microRNAs (miRNAs) and the RNA subtype of antisense oligonucleotides (ASOs) …