Evidence map›Paper›PMID 26229972›Full record

ArticleMolecular therapy. Methods & clinical development2015

Generation of a stable packaging cell line producing high-titer PPT-deleted integration-deficient lentiviral vectors.

Peirong Hu, Yedda Li, Mark S Sands, Thomas McCown, Tal Kafri

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Novel immortalized human vocal fold epithelial cell line: In vitro tool for mucosal biology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  6. Review
  7. Article
  8. Article
  9. In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  10. Article
  11. Review
  12. Review
  13. Production of lentiviral vectors.Molecular therapy. Methods & clinical development · 2016
    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

5 authors at 2 institutions in 1 country.

Peirong HuGene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA.
Yedda LiDepartment of Internal Medicine, Washington University School of Medicine , St. Louis, Missouri, USA.
Mark S SandsDepartment of Internal Medicine, Washington University School of Medicine , St. Louis, Missouri, USA ; Genetics, Washington University School of Medicine , St. Louis, Missouri, USA.
Thomas McCownGene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA ; Department of Psychiatry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA.
Tal KafriGene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA.
University of North Carolina at Chapel Hill · USWashington University in St. Louis · US

Funding

PRE-AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGYT32HL007088 · NHLBI · WASHINGTON UNIVERSITY · PI Grant Anthony Challen, Stephen Oh · 1985 to 2026
$14.1M
Nonintegrating Lentiviral Vectors Towards Clinical TrialsR01DK058702 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2001 to 2019
$5.0M
Lentiviral Vector-Based Gene Therapy and The Host Genetic BackgroundR01HL128119 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2015 to 2018
$3.0M
Novel Viral Vector Delivery for Efficient ShRNA ExpressionR21HL086406 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2006 to 2007
$396k
NHLBI NIH HHS R01 HL128119NHLBI NIH HHS R21 HL086406NHLBI NIH HHS T32 HL007088NIDDK NIH HHS R01 DK058702
6 · The paper itself

Abstract

The risk of insertional mutagenesis inherent to all integrating exogenous expression cassettes was the impetus for the development of various integration-defective lentiviral vector (IDLV) systems. These systems were successfully employed in a plethora of preclinical applications, underscoring their clinical potential. However, current production of IDLVs by transient plasmid transfection is not optimal for large-scale production of clinical grade vectors. Here, we describe the development of the first tetracycline-inducible stable IDLV packaging cell line comprising the D64E integrase mutant and the VSV-G envelope protein. A conditional self-inactivating (cSIN) vector and a novel polypurine tract (PPT)-deleted vector were incorporated into the newly developed stable packaging cell line by transduction and stable transfection, respectively. High-titer (~10(7) infectious units (IU)/ml) cSIN vectors were routinely generated. Furthermore, screening of single-cell clones stably transfected with PPT-deleted vector DNA resulted in the identification of highly efficient producer cell lines generating IDLV titers higher than 10(8) IU/mL, which upon concentration increased to 10(10) IU/ml. IDLVs generated by stable producer lines efficiently transduce CNS tissues of rodents. Overall, the availability of high-titer IDLV lentivirus packaging cell line described here will significantly facilitate IDLV-based basic science research, as well as preclinical and clinical applications.

Identifiers

PMID26229972
PMCPMC4510976
OpenAlexW1791343928

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.