Evidence map›Paper›PMID 25541967›Full record

ArticlePloS one2014

CCR5 gene disruption via lentiviral vectors expressing Cas9 and single guided RNA renders cells resistant to HIV-1 infection.

Weiming Wang, Chaobaihui Ye, Jingjing Liu, Di Zhang, Jason T Kimata, Paul Zhou

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

115 citing papers in PubMed, 191 citations in OpenAlex.

  1. Review
  2. Review
  3. Searching for a HIV-1 Cure.Theranostics · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Genome Editing in CAR-T Cells Using CRISPR/Cas9 Technology.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022
    Review
  17. Therapeutic Application of Genome Editing Technologies in Viral Diseases.International journal of molecular sciences · 2022
    Review
  18. Review
  19. Article
  20. Review

55 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

6 authors at 4 institutions in 2 countries.

Weiming WangThe Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025.
Chaobaihui YeThe Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025.
Jingjing LiuThe Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025.
Di ZhangBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China 200030.
Jason T KimataDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030.
Paul ZhouThe Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025.
Chinese Academy of Sciences · CNBaylor College of Medicine · USInstitut Pasteur of Shanghai · CNShanghai Jiao Tong University · CN

Funding

Virology CoreP30AI036211 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI BUTEL, JANET S · 1994 to 2015
$21.7M
Inhibition of HIV by GPI-anchored Antibody DerivativesR01AI106574 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI KIMATA, JASON T. · 2013 to 2015
$600k
NIAID NIH HHS AI106574NIAID NIH HHS P30 AI036211NIAID NIH HHS P30AI036211NIAID NIH HHS R01 AI106574
6 · The paper itself

Abstract

CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1.

Indexed as

Base SequenceCell LineCRISPR-Associated ProteinsGenetic EngineeringGenetic TherapyGenetic VectorsHIV-1HIV InfectionsHumansLentivirusReceptors, CCR5RNA, Guide, CRISPR-Cas SystemsTransduction, GeneticVirus InternalizationCRISPR-Associated ProteinsReceptors, CCR5RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID25541967
PMCPMC4277423
OpenAlexW2074350814

What OpenQuestion holds

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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 OpenQuestion graph.