ArticleMolecular therapy. Nucleic acids2023
A bimolecular modification strategy for developing long-lasting bone anabolic aptamer.
Article in Molecular therapy. Nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- Aptamer-Based Platforms for Human Aging Biomarkers: Multiplexed Proteomics, Biosensors and Translational Perspectives.International journal of molecular sciences · 2026Review
- AI-powered therapeutic aptamer drug discovery: Targeting the CT-domain of CTGF for duchenne muscular dystrophy.Acta pharmaceutica Sinica. B · 2026Article
- Blocking interaction of sclerostin loop3 with osteoblastic LRP4 counteracts bone loss without increasing arterial stiffness during mechanical unloading.Journal of orthopaedic translation · 2026Article
- Generative Artificial Intelligence Optimization of Albumin Binders: Coumarin and Fatty Acid Derivatives.Journal of chemical information and modeling · 2026Article
- Intracellular sclerostin promotes tumor progression and metastasis as a potential therapeutic target in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Myostatin Research: From Molecular Understanding to Clinical Translation for Musculoskeletal and Metabolic Disorders.International journal of molecular sciences · 2026Review
- Computational Study on Potentially Active Antibacterial Compounds in Secondary Metabolites of Extremophilic Microorganisms.ChemistryOpen · 2026Article
- Adipocytic sclerostin loop3-LRP4 interaction required by sclerostin to impair whole-body lipid and glucose metabolism.Nature communications · 2026Article
- Dual-Mechanism Aptamer-Drug Complex Overcomes Paclitaxel Resistance in Ovarian Cancer via Structural Constraint and Telomerase Inhibition.Research (Washington, D.C.) · 2026Article
- Article
- Novel Aptamers Targeting Sclerostin Loop3 Improve Skeletal and Muscle Properties Without Adverse Cardiovascular Effects in Orchiectomized Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Wolf in Sheep's Clothing: Taming Cancer's Resistance with Human Serum Albumin?International journal of nanomedicine · 2025Review
- Peptide Aptamer-Paclitaxel Conjugates for Tumor Targeted Therapy.Pharmaceutics · 2024Review
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular weight of nucleic acid aptamers (20 kDa) is lower than the cutoff threshold of the renal filtration (30-50 kDa), resulting in a very short half-life, which dramatically limits their druggability. To address this, we utilized 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(4-hydroxy-2-oxo-2H-chromen-6-yl)propenamide (HC) and 12-((2,5-dioxopyrrolidin-1-yl)oxy)-12-oxododecanoic acid (DA), two newly designed coupling agents, for synergistic binding to human serum albumin (HSA). Both HC and DA are conjugated to a bone anabolic aptamer (Apc001) against sclerostin to form an Apc001OC conjugate with high binding affinity to HSA. Notably, HC and DA could synergistically facilitate prolonging the half-life of the conjugated Apc001 and promoting its bone anabolic potential. Using the designed blocking peptides, the mechanism studies indicate that the synergistic effect of HC-DA on pharmacokinetics and bone anabolic potential of the conjugated Apc001 is achieved via their synergistic binding to HSA. Moreover, biweekly Apc001OC at 50 mg/kg shows comparable bone anabolic potential to the marketed sclerostin antibody given weekly at 25 mg/kg. This proposed bimolecular modification strategy could help address the druggability challenge for aptamers with a short half-life.
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