Evidence map›Paper›PMID 25893217›Full record

ArticleMOJ immunology2014

HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the Proviral Quasispecies in Reservoirs to Achieve a Cure.

Will Dampier, Michael R Nonnemacher, Neil T Sullivan, Jeffrey M Jacobson, Brian Wigdahl

Abstract read
In one paragraph

Article in MOJ immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
–field-weighted citation impact
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

42 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. HIV-1 cure strategies: why CRISPR?Expert opinion on biological therapy · 2021
    Review
  14. Broadly active zinc finger protein-guided transcriptional activation of HIV-1.Molecular therapy. Methods & clinical development · 2021
    Article
  15. Review
  16. The Use of CRISPR/Cas9 as a Tool to Study Human Infectious Viruses.Frontiers in cellular and infection microbiology · 2021
    Review
  17. Article
  18. Review
  19. MultiplexedViruses · 2020
    Article
  20. Article
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

5 authors.

Will DampierDepartment of Microbiology and Immunology, Drexel University College of Medicine, USA.
Michael R NonnemacherDepartment of Microbiology and Immunology, Drexel University College of Medicine, USA.
Neil T SullivanDepartment of Microbiology and Immunology, Drexel University College of Medicine, USA.
Jeffrey M JacobsonDepartment of Microbiology and Immunology, Drexel University College of Medicine, USA ; Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, USA.
Brian WigdahlDepartment of Microbiology and Immunology, Drexel University College of Medicine, USA.

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Ilker Kudret Sariyer · 2011 to 2026
$24.9M
Interdisciplinary And Translational Research Training In NeurohivT32MH079785 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Kamel Khalili · 2008 to 2026
$5.4M
High Specificity HIV-1 Markers Predictive of Neuro-AIDSR01DA019807 · NIDA · DREXEL UNIVERSITY · PI WIGDAHL, BRIAN · 2004 to 2014
$5.1M
NEUROLOGICAL &LYMPHOID FACTORS IN HIV1 LTR ACTIVATIONR01NS032092 · NINDS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI WIGDAHL, BRIAN · 1993 to 2011
$3.9M
Co-evolution of HIV-1 Regulators in CNS DiseaseR01NS046263 · NINDS · DREXEL UNIVERSITY · PI WIGDAHL, BRIAN · 2004 to 2009
$1.8M
NIDA NIH HHS R01 DA019807NIMH NIH HHS P30 MH092177NIMH NIH HHS T32 MH079785NINDS NIH HHS R01 NS032092NINDS NIH HHS R01 NS046263
6 · The paper itself

Abstract

Recently several gene-editing technologies developed are being explored for their potential utility in providing new and unique treatments for HIV. One of these technologies is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9 system. This system is being explored for its utility against host genes important to HIV infection, namely the HIV coreceptor CCR5, and for excision of the integrated genome from infected cells by targeting selected genes or genomic regions, especially the HIV-1 promoter or long terminal repeat (LTR). One of the major hurdles with the development of this technology for use in patients is defining the LTR sequence spectrum within the viral quasispecies present in the integrated virus and how that effects the number of guide RNAs (gRNAs) required to completely excise all proviral genomes. In this study, the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort was utilized to demonstrate that [1] the predominant sequence of the integrated proviral LTR within the PBMC compartment shows a decrease in the amount of variation per year regardless of the type of therapy; [2] predominant HIV-1 LTR sequence undergoes continued genetic change with respect to the predominant genotype in these cells for at least 6 years while on effective suppressive ART; [3] using next generation sequencing (NGS), to demonstrate that 4 of the 8 patient samples examined could have a complete gRNA regimen designed to target all known quasispecies; and [4] length of HAART therapy may reduce the number of gRNA required to eradicate provirus as shown by NGS and gRNA design for longitudinal samples of patient A0017 in the CARES cohort. Overall, these studies demonstrate the feasibility of addressing at least one of the major technological challenges of CRISPR/Cas9-mediated HIV-1 proviral genome eradication involving the effective targeting of all viral quasispecies in a given patient sample.

Indexed as

CRISPR/cas9excisionguide RNAHIVmemory T cells

Identifiers

PMID25893217
PMCPMC4399856

What OpenQuestion holds

Textmetadata
LicenceTDM
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.