ArticleMolecular therapy. Nucleic acids2012
Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice.
Article in Molecular therapy. Nucleic acids, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 68 citations in OpenAlex.
- IGF1R-targeted delivery of a bridged nucleic acid oligonucleotide-peptide conjugate for microRNA-21 inhibition in triple-negative breast cancer.NAR cancer · 2025Article
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Article
- Does Genotype Affect the Efficacy of PCSK9 Inhibitors in the Treatment of Familial Hypercholesterolemia?Cardiovascular drugs and therapy · 2025Review
- Novel strategy of liver cancer treatment with modified antisense oligonucleotides targeting human vasohibin-2.Cancer science · 2023Article
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- The Clinical Importance of Differentiating Monogenic Familial Hypercholesterolemia from Polygenic Hypercholesterolemia.Current cardiology reports · 2022Review
- Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications.Frontiers in cell and developmental biology · 2022Review
- Drug discovery and development scheme for liver-targeting bridged nucleic acid antisense oligonucleotides.Molecular therapy. Nucleic acids · 2021Article
- Bridged Nucleic Acids Reloaded.Molecules (Basel, Switzerland) · 2019Review
- Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Non-antibody Approaches to Proprotein Convertase Subtilisin Kexin 9 Inhibition: siRNA, Antisense Oligonucleotides, Adnectins, Vaccination, and New Attempts at Small-Molecule Inhibitors Based on New Discoveries.Frontiers in cardiovascular medicine · 2018Review
- BNAACS chemical biology · 2017Article
- PCSK9 Mutations in Familial Hypercholesterolemia: from a Groundbreaking Discovery to Anti-PCSK9 Therapies.Current atherosclerosis reports · 2017Review
- Lipid Lowering Therapy and Circulating PCSK9 Concentration.Journal of atherosclerosis and thrombosis · 2017Review
- Pathological and molecular analyses of atherosclerotic lesions in ApoE-knockout mice.Medical molecular morphology · 2017Article
- Development of Antisense Drugs for Dyslipidemia.Journal of atherosclerosis and thrombosis · 2016Review
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation.The Journal of biological chemistry · 2016Article
- Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes.Biology methods & protocols · 2016Article
- Inhibition of AAC(6')-Ib-mediated resistance to amikacin in Acinetobacter baumannii by an antisense peptide-conjugated 2',4'-bridged nucleic acid-NC-DNA hybrid oligomer.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2',4'-BNA (also called as locked nucleic acid (LNA)) and 2',4'-BNA(NC) chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all of the BNA-AONs induce dose-dependent reductions in PCSK9 messenger RNA (mRNA) levels concomitantly with increases in LDLR protein levels. BNA-AONs were administered to atherogenic diet-fed C57BL/6J mice twice weekly for 6 weeks; 2',4'-BNA-AON that targeted murine PCSK9 induced a dose-dependent reduction in hepatic PCSK9 mRNA and LDL cholesterol (LDL-C); the 43% reduction of serum LDL-C was achieved at a dose of 20 mg/kg/injection with only moderate increases in toxicological indicators. In addition, the serum high-density lipoprotein cholesterol (HDL-C) levels increased. These results support antisense inhibition of PCSK9 as a potential therapeutic approach. When compared with 2',4'-BNA-AON, 2',4'-BNA(NC)-AON showed an earlier LDL-C-lowering effect and was more tolerable in mice. Our results validate the optimization of 2',4'-BNA(NC)-based anti-PCSK9 antisense molecules to produce a promising therapeutic agent for the treatment of hypercholesterolemia.
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Registered trials
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.