Evidence map›Paper›PMID 24927590›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection.

Lin Ye, Jiaming Wang, Ashley I Beyer, Fernando Teque, Thomas J Cradick, Zhongxia Qi, Judy C Chang, Gang Bao, Marcus O Muench, Jingwei Yu and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed
20.8field-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

170 citing papers in PubMed, 316 citations in OpenAlex.

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  8. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
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  15. CRISPR/Cas9-mediated genome editing technique to control fall armyworm (Physiology and molecular biology of plants : an international journal of functional plant biology · 2024
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  20. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review

110 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

12 authors at 4 institutions in 2 countries.

Lin YeDepartment of Medicine and Institute for Human Genetics, lin.ye@ucsf.edu yw.kan@ucsf.edu.
Jiaming WangDepartment of Medicine and Institute for Human Genetics,Department of Laboratory Medicine, and.
Ashley I BeyerBlood Systems Research Institute, San Francisco, CA 94118; and.
Fernando TequeDepartment of Medicine and Institute for Human Genetics,Division of Hematology/Oncology, University of California, San Francisco, CA 94143;
Thomas J CradickDepartment of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322.
Zhongxia QiDepartment of Laboratory Medicine, and.
Judy C ChangDepartment of Medicine and Institute for Human Genetics.
Gang BaoDepartment of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322.
Marcus O MuenchDepartment of Laboratory Medicine, andBlood Systems Research Institute, San Francisco, CA 94118; andThe Liver Center.
Jingwei YuDepartment of Laboratory Medicine, and.
Jay A LevyDivision of Hematology/Oncology, University of California, San Francisco, CA 94143;
Yuet Wai KanDepartment of Medicine and Institute for Human Genetics,Department of Laboratory Medicine, and lin.ye@ucsf.edu yw.kan@ucsf.edu.
Institute of Human Genetics · PLBlood Systems Research Institute · USGeorgia Institute of Technology · USUniversity of California, San Francisco · US

Funding

Reprogramming iPS Cells with Exogenous and Endogenous Transcription Factor GenesP01DK088760 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRUENERT, DIETER C · 2011 to 2015
$6.5M
HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem CellsR01AI102825 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEVY, JAY A · 2014 to 2016
$2.0M
HIV cure with CCR5 (-) human IPS hematopoietic stem cellsR56AI102825 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEVY, JAY A · 2012 to 2012
$518k
NIAID NIH HHS AI 102825NIAID NIH HHS R01 AI102825NIAID NIH HHS R56 AI102825NIDDK NIH HHS P01 DK088760NIDDK NIH HHS P01DK088760
6 · The paper itself

Abstract

Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.

Indexed as

Blotting, SouthernCell DifferentiationCells, CulturedClustered Regularly Interspaced Short Palindromic RepeatsDeoxyribonucleasesDisease ResistanceDNA PrimersFluorescent Antibody TechniqueGenetic EngineeringGenetic VectorsHIV InfectionsHumansInduced Pluripotent Stem CellsMacrophagesMonocytesMutagenesisCCR5 protein, humanDeoxyribonucleasesDNA PrimersReceptors, CCR5Transposasescellular therapyhomologous recombinationoff-site targetTTAA site

Identifiers

PMID24927590
PMCPMC4084478
OpenAlexW2053763799

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.