Evidence map›Paper›PMID 25946221›Full record

ArticlePloS one2015

Damaging the Integrated HIV Proviral DNA with TALENs.

Christy L Strong, Horacio P Guerra, Kiran R Mathew, Nervik Roy, Lacy R Simpson, Martin R Schiller

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  5. Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  6. HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022
    Review
  7. Therapeutic Application of Genome Editing Technologies in Viral Diseases.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Review
  10. TALENs-an indispensable tool in the era of CRISPR: a mini review.Journal, genetic engineering & biotechnology · 2021
    Review
  11. Review
  12. Review
  13. Can Designer Indels Be Tailored by Gene Editing?: Can Indels Be Customized?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019
    Article
  14. Article
  15. Article
  16. Review
  17. Novel AIDS therapies based on gene editing.Cellular and molecular life sciences : CMLS · 2017
    Review
  18. Review
  19. Nuclear landscape of HIV-1 infection and integration.Nature reviews. Microbiology · 2017
    Review
  20. 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

6 authors at 1 institution in 1 country.

Christy L StrongNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
Horacio P GuerraNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
Kiran R MathewNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
Nervik RoyNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
Lacy R SimpsonNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
Martin R SchillerNevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States of America.
University of Nevada, Las Vegas · US

Funding

Outreach/Diversity/Pipeline ProjectP20GM103440 · NIGMS · UNIVERSITY OF NEVADA RENO · PI Julia Petereit · 2012 to 2026
$58.0M
Kids Seek Cure For KidsR25DK078385 · NIDDK · CHILDREN'S HOSPITAL OF LOS ANGELES · PI BOGENMANN, EMIL · 2007 to 2021
$3.4M
NIDDK NIH HHS R25 DK078385NIDDK NIH HHS R25-DK078385NIGMS NIH HHS P20 GM103440NIGMS NIH HHS P20-GM103440
6 · The paper itself

Abstract

HIV-1 integrates its proviral DNA genome into the host genome, presenting barriers for virus eradication. Several new gene-editing technologies have emerged that could potentially be used to damage integrated proviral DNA. In this study, we use transcription activator-like effector nucleases (TALENs) to target a highly conserved sequence in the transactivation response element (TAR) of the HIV-1 proviral DNA. We demonstrated that TALENs cleave a DNA template with the HIV-1 proviral target site in vitro. A GFP reporter, under control of HIV-1 TAR, was efficiently inactivated by mutations introduced by transfection of TALEN plasmids. When infected cells containing the full-length integrated HIV-1 proviral DNA were transfected with TALENs, the TAR region accumulated indels. When one of these mutants was tested, the mutated HIV-1 proviral DNA was incapable of producing detectable Gag expression. TALEN variants engineered for degenerate recognition of select nucleotide positions also cleaved proviral DNA in vitro and the full-length integrated proviral DNA genome in living cells. These results suggest a possible design strategy for the therapeutic considerations of incomplete target sequence conservation and acquired resistance mutations. We have established a new strategy for damaging integrated HIV proviral DNA that may have future potential for HIV-1 proviral DNA eradication.

Indexed as

Binding SitesCell Line, TumorConserved SequenceDNA DamageDNA Restriction EnzymesDNA, ViralHeLa CellsHIV-1HIV InfectionsHumansProvirusesResponse ElementsVirus IntegrationDNA Restriction EnzymesDNA, Viral

Identifiers

PMID25946221
PMCPMC4422436
OpenAlexW1913766292

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.