Evidence map›Paper›PMID 26258894›Full record

ArticleNature communications2015

DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing.

Kazutaka Nishina, Wenying Piao, Kie Yoshida-Tanaka, Yumiko Sujino, Tomoko Nishina, Tsuyoshi Yamamoto, Keiko Nitta, Kotaro Yoshioka, Hiroya Kuwahara, Hidenori Yasuhara and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
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.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 126 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. DNA/RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Chondroitin Sulfate-Coated Heteroduplex-Molecular Spherical Nucleic Acids.Chembiochem : a European journal of chemical biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023
    Review
  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

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

22 authors at 7 institutions in 2 countries.

Kazutaka Nishina1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Wenying Piao1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Kie Yoshida-Tanaka1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Yumiko Sujino1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Tomoko Nishina1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Tsuyoshi YamamotoBioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Keiko NittaDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kotaro Yoshioka1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Hiroya Kuwahara1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Hidenori YasuharaBioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Takeshi BabaBioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Fumiko OnoThe Corporation for Production and Research of Laboratory Primates, 1-16-2 Sakura, Tsukuba-shi, Ibaraki 305-0003, Japan.
Kanjiro MiyataDivision of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Koichi MiyakeDepartment of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Punit P SethIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, California 92010, USA.
Audrey LowIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, California 92010, USA.
Masayuki YoshidaDepartment of Life Science and Medical Ethics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
C Frank BennettIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, California 92010, USA.
Kazunori Kataoka1] Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Hidehiro MizusawaDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Satoshi Obika1] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan [2] Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Takanori Yokota1] Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan [2] Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Tokyo Medical and Dental University · JPOsaka University · JPIonis Pharmaceuticals (United States) · USJapan Science and Technology Agency · JPThe University of Tokyo · JPCorporation for Production and Research of Laboratory Primates · JPNippon Medical School · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single-stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an α-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field.

Indexed as

Oligonucleotidesalpha-TocopherolAnimalsApolipoproteins BBase SequenceDietary FatsGene SilencingHumansHypercholesterolemiaMacaca fascicularisMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNucleic Acid HeteroduplexesRNA, Messengeralpha-TocopherolApolipoproteins BDietary FatsNucleic Acid HeteroduplexesOligonucleotidesRNA, Messenger

Identifiers

PMID26258894
PMCPMC4918363
OpenAlexW1169770544

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.