Evidence map›Paper›PMID 27460639›Full record

ArticleScientific reports2016

Novel HDAd/EBV Reprogramming Vector and Highly Efficient Ad/CRISPR-Cas Sickle Cell Disease Gene Correction.

Chao Li, Lei Ding, Chiao-Wang Sun, Li-Chen Wu, Dewang Zhou, Kevin M Pawlik, Alireza Khodadadi-Jamayran, Erik Westin, Frederick D Goldman, Tim M Townes

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Genome editing strategies for targeted correction of β-globin mutation in sickle cell disease: From bench to bedside.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  18. Long-Term Engraftment and Fetal Globin Induction uponMolecular therapy. Methods & clinical development · 2017
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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

10 authors at 1 institution in 1 country.

Chao LiDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Lei DingDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Chiao-Wang SunDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Li-Chen WuDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Dewang ZhouDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Kevin M PawlikDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Alireza Khodadadi-JamayranUAB Stem Cell Institute, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Erik WestinDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Frederick D GoldmanUAB Stem Cell Institute, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
Tim M TownesDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA.
University of Alabama at Birmingham · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR/Cas enhanced correction of the sickle cell disease (SCD) genetic defect in patient-specific induced Pluripotent Stem Cells (iPSCs) provides a potential gene therapy for this debilitating disease. An advantage of this approach is that corrected iPSCs that are free of off-target modifications can be identified before differentiating the cells into hematopoietic progenitors for transplantation. In order for this approach to be practical, iPSC generation must be rapid and efficient. Therefore, we developed a novel helper-dependent adenovirus/Epstein-Barr virus (HDAd/EBV) hybrid reprogramming vector, rCLAE-R6, that delivers six reprogramming factors episomally. HDAd/EBV transduction of keratinocytes from SCD patients resulted in footprint-free iPSCs with high efficiency. Subsequently, the sickle mutation was corrected by delivering CRISPR/Cas9 with adenovirus followed by nucleoporation with a 70 nt single-stranded oligodeoxynucleotide (ssODN) correction template. Correction efficiencies of up to 67.9% (β(A)/[β(S)+β(A)]) were obtained. Whole-genome sequencing (WGS) of corrected iPSC lines demonstrated no CRISPR/Cas modifications in 1467 potential off-target sites and no modifications in tumor suppressor genes or other genes associated with pathologies. These results demonstrate that adenoviral delivery of reprogramming factors and CRISPR/Cas provides a rapid and efficient method of deriving gene-corrected, patient-specific iPSCs for therapeutic applications.

Indexed as

Genetic TherapyAdenoviridaeAnemia, Sickle CellBase SequenceCell LineCRISPR-Cas SystemsGenetic VectorsHelper VirusesHerpesvirus 4, HumanHomozygoteHumansInduced Pluripotent Stem Cells

Identifiers

PMID27460639
PMCPMC4961958
OpenAlexW2477684766

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.