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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 …
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 …
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 …
Chemical modifications are necessary to ensure the metabolic stability and efficacy of
oligonucleotide-based therapeutics. Here, we describe analyses of the α-(l)-threofuranosyl …
oligonucleotide-based therapeutics. Here, we describe analyses of the α-(l)-threofuranosyl …
Silencing or stimulation? siRNA delivery and the immune system
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 …
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 …
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 …
induced silencing complex (RISC). Presence of 5′‐phosphate (5′‐P) is reported to be …
Specificity of oligonucleotide gene therapy (OGT) agents
Oligonucleotide gene therapy (OGT) agents (eg antisense, deoxyribozymes, siRNA and
CRISPR/Cas) are promising therapeutic tools. Despite extensive efforts, only few OGT drugs …
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
Abstract 5΄-Vinylphosphonate modification of siRNAs protects them from phosphatases, and
improves silencing activity. Here, we show that 5΄-vinylphosphonate confers novel …
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 …
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
Three types of highly promising small RNA therapeutics, namely, small interfering RNAs
(siRNAs), microRNAs (miRNAs) and the RNA subtype of antisense oligonucleotides (ASOs) …
(siRNAs), microRNAs (miRNAs) and the RNA subtype of antisense oligonucleotides (ASOs) …