Evidence map›Paper›PMID 34937876›Full record

ArticleNature communications2021

DNA/RNA heteroduplex oligonucleotide technology for regulating lymphocytes in vivo.

Masaki Ohyagi, Tetsuya Nagata, Kensuke Ihara, Kie Yoshida-Tanaka, Rieko Nishi, Haruka Miyata, Aya Abe, Yo Mabuchi, Chihiro Akazawa, Takanori Yokota

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. DNA/RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Article
  5. Molecular therapy. Methods & clinical development · 2025
    Article
  6. RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
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

10 authors at 1 institution in 1 country.

Masaki OhyagiDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.ORCID http://orcid.org/0000-0002-6009-450X
Tetsuya NagataDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. t-naga.nuro@tmd.ac.jp.ORCID http://orcid.org/0000-0003-4111-2693
Kensuke IharaDepartment of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.ORCID http://orcid.org/0000-0002-2436-9588
Kie Yoshida-TanakaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Rieko NishiDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.ORCID http://orcid.org/0000-0003-2733-0053
Haruka MiyataDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Aya AbeDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Yo MabuchiDepartment of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8008-3966
Chihiro AkazawaDepartment of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Takanori YokotaDepartment of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. tak-yokota.nuro@tmd.ac.jp.ORCID http://orcid.org/0000-0002-6490-3263
Tokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Manipulating lymphocyte functions with gene silencing approaches is promising for treating autoimmunity, inflammation, and cancer. Although oligonucleotide therapy has been proven to be successful in treating several conditions, efficient in vivo delivery of oligonucleotide to lymphocyte populations remains a challenge. Here, we demonstrate that intravenous injection of a heteroduplex oligonucleotide (HDO), comprised of an antisense oligonucleotide (ASO) and its complementary RNA conjugated to α-tocopherol, silences lymphocyte endogenous gene expression with higher potency, efficacy, and longer retention time than ASOs. Importantly, reduction of Itga4 by HDO ameliorates symptoms in both adoptive transfer and active experimental autoimmune encephalomyelitis models. Our findings reveal the advantages of HDO with enhanced gene knockdown effect and different delivery mechanisms compared with ASO. Thus, regulation of lymphocyte functions by HDO is a potential therapeutic option for immune-mediated diseases.

Indexed as

Administration, IntravenousAdoptive TransferAnimalsDemyelinating DiseasesEncephalomyelitis, Autoimmune, ExperimentalEndocytosisFemaleGene Expression RegulationGene SilencingGraft vs Host DiseaseHumansIntegrin alpha4Jurkat CellsLymphocytesMaleMiceIntegrin alpha4Malat1 long non-coding RNA, mouseNucleic Acid HeteroduplexesOligonucleotidesRNARNA, Long NoncodingRNA, Messenger

Identifiers

PMID34937876
PMCPMC8695577
OpenAlexW4200319050

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.