ArticleNucleic acids research2020
Chimeric siRNAs with chemically modified pentofuranose and hexopyranose nucleotides: altritol-nucleotide (ANA) containing GalNAc-siRNA conjugates: in vitro and in vivo RNAi activity and resistance to 5'-exonuclease.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 42 citations in OpenAlex.
- Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia.Nucleic acids research · 2025Article
- Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.Nucleic acids research · 2025Article
- The XNA alphabet.Nucleic acids research · 2025Review
- Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.Nature biotechnology · 2025Article
- An epimer of threose nucleic acid enhances oligonucleotide exonuclease resistance through end capping.Communications chemistry · 2025Article
- Improving the potency prediction for chemically modified siRNAs through insights from molecular modeling of individual sequence positions.Molecular therapy. Nucleic acids · 2025Article
- Article
- Two Birds with One Stone: A Novel Dithiomaleimide-Based GalNAc-siRNA Conjugate Enabling Good siRNA Delivery and Traceability.Molecules (Basel, Switzerland) · 2023Article
- Molecular elements: novel approaches for molecular building.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Evaluation of 3'-phosphate as a transient protecting group for controlled enzymatic synthesis of DNA and XNA oligonucleotides.Communications chemistry · 2022Article
- siRNA Seed Region Is Divided into Two Functionally Different Domains in RNA Interference in Response to 2'-OMe Modifications.ACS omega · 2022Article
- Advances in siRNA therapeutics and synergistic effect on siRNA activity using emerging dual ribose modifications.RNA biology · 2022Review
- Feasibility of cRGD conjugation at 5'-antisense strand of siRNA by phosphodiester linkage extension.Molecular therapy. Nucleic acids · 2021Article
- siRNAs containing 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2'-F-NMC NTPs.Nucleic acids research · 2021Article
- Synthesis and evaluation of modified siRNA molecules containing a novel glucose derivative.RSC advances · 2021Article
- Recent Advances in the Development of Exogenous dsRNA for the Induction of RNA Interference in Cancer Therapy.Molecules (Basel, Switzerland) · 2021Review
- Chemical strategies for strand selection in short-interfering RNAs.RSC advances · 2021Review
- Beyond ribose and phosphate: Selected nucleic acid modifications for structure-function investigations and therapeutic applications.Beilstein journal of organic chemistry · 2021Review
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Review
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this report, we investigated the hexopyranose chemical modification Altriol Nucleic Acid (ANA) within small interfering RNA (siRNA) duplexes that were otherwise fully modified with the 2'-deoxy-2'-fluoro and 2'-O-methyl pentofuranose chemical modifications. The siRNAs were designed to silence the transthyretin (Ttr) gene and were conjugated to a trivalent N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. Sense and antisense strands of the parent duplex were synthesized with single ANA residues at each position on the strand, and the resulting siRNAs were evaluated for their ability to inhibit Ttr mRNA expression in vitro. Although ANA residues were detrimental at the 5' end of the antisense strand, the siRNAs with ANA at position 6 or 7 in the seed region had activity comparable to the parent. The siRNA with ANA at position 7 in the seed region was active in a mouse model. An Oligonucleotide with ANA at the 5' end was more stable in the presence of 5'-exonuclease than an oligonucleotide of the same sequence and chemical composition without the ANA modification. Modeling studies provide insight into the origins of regiospecific changes in potency of siRNAs and the increased protection against 5'-exonuclease degradation afforded by the ANA modification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.