Evidence map›Paper›PMID 22429108›Full record

ArticleHuman gene therapy2012

Zinc finger protein designed to target 2-long terminal repeat junctions interferes with human immunodeficiency virus integration.

Supachai Sakkhachornphop, Carlos F Barbas, Rassamee Keawvichit, Kanlaya Wongworapat, Chatchai Tayapiwatana

Abstract read
In one paragraph

Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Stem cell-based therapies for HIV/AIDS.Advanced drug delivery reviews · 2016
    Review
  10. Article
  11. Engineering T Cells to Functionally Cure HIV-1 Infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. 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 at 2 institutions in 1 country.

Supachai SakkhachornphopDivision of Clinical Immunology, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand.
Carlos F Barbas
Rassamee Keawvichit
Kanlaya Wongworapat
Chatchai Tayapiwatana
Chiang Mai University · THNational Science and Technology Development Agency · TH

Funding

Transcriptional Blockades of HIV-1R01GM065059 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI BARBAS, CARLOS F · 2003 to 2010
$2.8M
NIGMS NIH HHS GM065059
6 · The paper itself

Abstract

Integration of the human immunodeficiency virus type 1 (HIV-1) genome into the host chromosome is a vital step in the HIV life cycle. The highly conserved cytosine-adenine (CA) dinucleotide sequence immediately upstream of the cleavage site is crucial for integrase (IN) activity. As this viral enzyme has an important role early in the HIV-1 replication cycle, interference with the IN substrate has become an attractive strategy for therapeutic intervention. We demonstrated that a designed zinc finger protein (ZFP) fused to green fluorescent protein (GFP) targets the 2-long terminal repeat (2-LTR) circle junctions of HIV-1 DNA with nanomolar affinity. We report now that 2LTRZFP-GFP stably transduced into 293T cells interfered with the expression of vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral red fluorescent protein (RFP), as shown by the suppression of RFP expression. We also used a third-generation lentiviral vector and pCEP4 expression vector to deliver the 2LTRZFP-GFP transgene into human T-lymphocytic cells, and a stable cell line for long-term expression studies was selected for HIV-1 challenge. HIV-1 integration and replication were inhibited as measured by Alu-gag real-time PCR and p24 antigen assay. In addition, the molecular activity of 2LTRZFP-GFP was evaluated in peripheral blood mononuclear cells. The results were confirmed by Alu-gag real-time PCR for integration interference. We suggest that the expression of 2LTRZFP-GFP limited viral integration on intracellular immunization, and that it has potential for use in HIV gene therapy in the future.

Indexed as

HIV Long Terminal RepeatVirus IntegrationZinc FingersCell LineDNA-Binding ProteinsGenetic TherapyGreen Fluorescent ProteinsHIV-1HIV InfectionsHumansT-LymphocytesTransduction, GeneticDNA-Binding ProteinsGreen Fluorescent Proteins

Identifiers

PMID22429108
PMCPMC3440019
OpenAlexW2137631861

What OpenQuestion holds

Textmetadata
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.