Evidence map›Paper›PMID 27404981›Full record

ArticleScientific reports2016

Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9.

Kristine E Yoder, Ralf Bundschuh

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 102 citations in OpenAlex.

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  9. Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  10. Review
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  12. Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Review
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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

2 authors at 2 institutions in 1 country.

Kristine E YoderDepartment of Molecular Virology, Immunology and Medical Genetics, Center for Retrovirus Research, The Ohio State University Medical Center, Columbus, Ohio, USA.
Ralf BundschuhDepartment of Physics, Department of Chemistry and Biochemistry, Division of Hematology, Department of Internal Medicine, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
The Ohio State University · USThe Ohio State University Wexner Medical Center · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI WANCAI YANG · 1985 to 2026
$132.3M
Studies of the molecular mechanism of retroviral integrationR21AI099854 · NIAID · OHIO STATE UNIVERSITY · PI FISHEL, RICHARD, YODER, KRISTINE E · 2013 to 2014
$422k
NCI NIH HHS P30 CA016058NIAID NIH HHS R21 AI099854
6 · The paper itself

Abstract

CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsCD4-Positive T-LymphocytesCell LineDNA Breaks, Double-StrandedGene EditingGene TargetingHIV-1HIV InfectionsHumansMutationRNA, Guide, CRISPR-Cas SystemsVirus ReplicationRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID27404981
PMCPMC4941621
OpenAlexW2469238969

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.