Evidence map›Paper›PMID 15280451›Full record

ArticleJournal of virology2004

Integrated self-inactivating lentiviral vectors produce full-length genomic transcripts competent for encapsidation and integration.

Aaron C Logan, Dennis L Haas, Tal Kafri, Donald B Kohn

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

39 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Gene therapy · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Emerging Gene Therapies for Genetic Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2017
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

4 authors at 3 institutions in 1 country.

Aaron C LoganDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Dennis L Haas
Tal Kafri
Donald B Kohn
Children's Hospital of Los Angeles · USUniversity of North Carolina at Chapel Hill · USUniversity of Southern California · US

Funding

TARGETING OF RETROVIRAL REPLICATION TO TUMORSP01CA059318 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KEDES, LAURENCE H · 1992 to 2005
$8.4M
Nonintegrating Lentiviral Vectors Towards Clinical TrialsR01DK058702 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2001 to 2019
$5.0M
VIROLOGY, IMMUNOLOGY &ONCOLOGY: MECHANISMS OF DISEASET32AI007078 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LAI, MICHAEL M.C. · 1985 to 2006
$1.1M
PROGRAM IN MOLECULAR ONCOLOGYT32CA009569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LIEBER, MICHAEL R · 1987 to 2002
$210k
NCI NIH HHS 1P01 CA59318NCI NIH HHS CA09569-13NCI NIH HHS P01 CA059318NCI NIH HHS T32 CA009569NIAID NIH HHS AI07078-18NIAID NIH HHS T32 AI007078NIDDK NIH HHS R01 DK058702NIDDK NIH HHS R01 DK58702-01
6 · The paper itself

Abstract

To make human immunodeficiency virus type 1 (HIV-1)-based vectors safer for use in the research and clinical setting, a significant modification to the HIV-1 genome has been the deletion of promoter and enhancer elements from the U3 region of the long terminal repeat (LTR). Vectors containing this deletion are thought to have no LTR-directed transcription and are called self-inactivating (SIN) lentivectors. Using four distinct approaches, we show that SIN lentivectors continue to have promoter activity near the 5' LTR, which is responsible for the production of full-length vector transcripts. To verify that transcripts derived from the LTR in SIN lentivectors are competent for encapsidation and integration, we transduced a lentiviral packaging cell line with a SIN lentivector and then observed the production of viable vector particles containing full-length SIN lentivector genomes. We have also attempted to identify sequences in the SIN lentivector which are responsible for transcriptional activation at the 5' LTR. Using different segments of the vector LTR and leader region in a promoter assay, we have determined that the residual promoter activity is contained entirely within the leader region and that, although this element is downstream of the transcription initiation site, it is capable of initiating transcription from the 5' end of R in the LTR. Mutation of leader region binding sites for the transcriptional activators downstream binding factor 1 (DBF1) and SP1 reduces transcription from the SIN LTR by up to 80%. Knowledge of the potential for mobilization of HIV-1-derived SIN lentivectors will be important for the design of future gene therapy trials with such vectors.

Indexed as

Genetic VectorsGenome, ViralTranscription, GeneticVirus IntegrationBase SequenceCell LineHIV-1HIV Long Terminal RepeatHumansMolecular Sequence DataPromoter Regions, GeneticTransduction, GeneticVirus Assembly

Identifiers

PMID15280451
PMCPMC479072
OpenAlexW2102549543

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.