Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
18 authors.
Sakino Matsuda-KawabataDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0009-0005-5784-3724
Tetsuya NagataDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0003-4111-2693
Mitsugu YanagidairaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0002-4694-6227
Kensuke IharaDepartment of Cardiovascular Medicine, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0002-2436-9588
Masaki OhyagiDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0002-6009-450X
Hidetoshi KaburagiDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0003-4272-6347
Kie Yoshida-TanakaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.
Asuka SasakiDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.
Aya AbeDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.
Satoe EbiharaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.
Juri HasegawaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0001-7799-4216
Nozomi ToideDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0009-0003-6201-3819
Masahiro OharaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0003-0344-251X
Mitsuru NaitoDepartment of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-8656 Tokyo, Japan.ORCID 0000-0002-4237-871X
Kanjiro MiyataDepartment of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-8656 Tokyo, Japan.ORCID 0000-0001-7044-190X
Kazuko TohDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0003-1448-7131
Fumika SakaueDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0003-1364-8730
Takanori YokotaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 Tokyo, Japan.ORCID 0000-0002-6490-3263
Funding
Advanced Biological Medicine JP20am0401006h0002Basic Science and Platform Technology Programs for Innovative Biological Medicine JP18am0301003h0005Discovering and Manufacturing Drugs for Next-Generation Treatment and Diagnosis JP21ae0121026h0001Early-Career Scientists 24K18251Japan Agency for Medical Research and DevelopmentJSPS 19H01016JSPS 22H00440Ministry of Education, Culture, Sports, Science and TechnologyTakeda Pharmaceutical CompanyTMDU Priority Research Areas
6 · The paper itself
Abstract
Recent advances in gapmer antisense oligonucleotides (ASOs) have led to the regulatory approval of ASO therapeutics that target the liver and central nervous system. Efficient delivery of gapmer ASOs to muscle tissue will further broaden their therapeutic applications. Here, we evaluated the knockdown activity of lipid-conjugated DNA/RNA heteroduplex oligonucleotides (HDOs) in muscle tissue. Cholesterol-conjugated HDO (Chol-HDO) exhibited effective gene suppression in both cardiac and skeletal muscles, outperforming unconjugated ASO and cholesterol-conjugated ASO (Chol-ASO). Chol-HDO and Chol-ASO showed greater binding to low-density lipoprotein (LDL); however, while Chol-ASO also exhibited enhanced binding to other serum proteins, Chol-HDO displayed weaker nonspecific interactions. Mechanistically, Chol-HDO enhanced cellular uptake through an LDL receptor-mediated mechanism. Moreover, subcellular distribution analysis revealed that the duplex structure of Chol-HDO promoted efficient nuclear delivery. Regarding safety, intravenous injection of Chol-ASO induced thrombocytopenia, whereas Chol-HDO mitigated this effect at the same dose. Ex vivo platelet activation assays confirmed that platelet activation was significantly more suppressed by Chol-HDO treatment than by Chol-ASO. Taken together, these results underscore the therapeutic potential of HDOs for safe and effective knockdown in muscle tissue, and provide a novel platform for the clinical development of gapmer ASO therapy for muscular disorders.
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.
Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles. · full record | OpenQuestion