Evidence map›Paper›PMID 12883534›Full record

ArticleGene therapy2003

Directed evolution of retroviruses activatable by tumour-associated matrix metalloproteases.

R M Schneider, Y Medvedovska, I Hartl, B Voelker, M P Chadwick, S J Russell, K Cichutek, C J Buchholz

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2003. 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
3.3field-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

16 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Physical, chemical, and synthetic virology: Reprogramming viruses as controllable nanodevices.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2019
    Review
  4. Stimulus-responsive viral vectors for controlled delivery of therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2017
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Molecular engineering of viral gene delivery vehicles.Annual review of biomedical engineering · 2008
    Review
  11. Article
  12. Review
  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

8 authors at 3 institutions in 3 countries.

R M SchneiderMedizinische Biotechnologie, Paul-Ehrlich-Institut, Langen, Germany.
Y Medvedovska
I Hartl
B Voelker
M P Chadwick
S J Russell
K Cichutek
C J Buchholz
Paul Ehrlich Institut · DEBiocompatibles (United Kingdom) · GBMayo Clinic in Arizona · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protease-activatable retroviral vectors offer the possibility of targeted gene transfer into cancer cells expressing a unique set of proteases as, for example, the matrix metalloproteases (MMPs). However, it is difficult to predict which substrate sequence will be optimally cleaved by a given tumour cell type. Therefore, we developed a novel approach that allows the selection of MMP-activatable retroviruses from libraries of viruses displaying combinatorially diversified protease substrates. Starting from a virus harbouring a standard MMP-2 substrate motif, after only two consecutive cycles of diversification and in vivo selection, MMP-activatable viruses were recovered. Biochemical characterization of the selected viruses revealed that their linker peptides showed a considerably increased sensitivity for MMP-2 cleavage, and interestingly also improved the particle incorporation rate of the Env protein. Owing to the optimized linker peptide, the selected viruses exhibited a greatly enhanced spreading efficiency through human fibrosarcoma cells, while having retained the dependency on MMP activation. Moreover, cell entry efficiency and virus titres were considerably improved as compared to the parental virus displaying the standard MMP-2 substrate. The results presented imply that retroviral protease substrate libraries allow the definition of MMP substrate specificities under in vivo conditions as well as the generation of optimally adapted tumour-specific viruses.

Indexed as

Evolution, MolecularCell LineGenetic EngineeringGenetic TherapyHumansMatrix MetalloproteinasesNeoplasmsPeptide LibraryRetroviridaeVirus ActivationMatrix MetalloproteinasesPeptide Library

Identifiers

PMID12883534
OpenAlexW2035701696

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.