Evidence map›Paper›PMID 21056576›Full record

ArticleJournal of molecular biology2011

Her2-specific multivalent adapters confer designed tropism to adenovirus for gene targeting.

Birgit Dreier, Galina Mikheeva, Natalya Belousova, Petra Parizek, Edgar Boczek, Ilian Jelesarov, Patrik Forrer, Andreas Plückthun, Victor Krasnykh

Abstract read
In one paragraph

Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Article
  3. FAP-retargeted Ad5 enables in vivo gene delivery to stromal cells in the tumor microenvironment.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  4. Targeted adenovirus-mediated transduction of human T cellsMolecular therapy. Methods & clinical development · 2023
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

9 authors at 1 institution in 1 country.

Birgit DreierDepartment of Biochemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
Galina Mikheeva
Natalya Belousova
Petra Parizek
Edgar Boczek
Ilian Jelesarov
Patrik Forrer
Andreas Plückthun
Victor Krasnykh
University of Zurich · CH

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Her2-targeted vectors for gene therapy of cancerR01CA116621 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KRASNYKH, VICTOR · 2005 to 2009
$1.6M
Multi-serotype adenovirus vector system for targeted gene delivery to tumorsR01CA128807 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KRASNYKH, VICTOR · 2009 to 2011
$949k
NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA16672NCI NIH HHS R01 CA116621NCI NIH HHS R01 CA128807
6 · The paper itself

Abstract

Adenoviruses (Ads) hold great promise as gene vectors for diagnostic or therapeutic applications. The native tropism of Ads must be modified to achieve disease site-specific gene delivery by Ad vectors and this should be done in a programmable way and with technology that can realistically be scaled up. To this end, we applied the technologies of designed ankyrin repeat proteins (DARPins) and ribosome display to develop a DARPin that binds the knob domain of the Ad fiber protein with low nanomolar affinity (K(D) 1.35 nM) and fused this protein with a DARPin specific for Her2, an established cell-surface biomarker of human cancers. The stability of the complex formed by this bispecific targeting adapter and the Ad virion resulted in insufficient gene transfer and was subsequently improved by increasing the valency of adapter-virus binding. In particular, we designed adapters that chelated the knob in a bivalent or trivalent fashion and showed that the efficacy of gene transfer by the adapter-Ad complex increased with the functional affinity of these molecules. This enabled efficient transduction at low stoichiometric adapter-to-fiber ratios. We confirmed the Her2 specificity of this transduction and its dependence on the Her2-binding DARPin component of the adapters. Even the adapter molecules with four fused DARPins could be produced and purified from Escherichia coli at very high levels. In principle, DARPins can be generated against any target and this adapter approach provides a versatile strategy for developing a broad range of disease-specific gene vectors.

Indexed as

Gene TargetingViral TropismAdenoviridaeAnkyrin RepeatCapsid ProteinsCells, CulturedErb-b2 Receptor Tyrosine KinasesGenetic VectorsHumansKidneyLuciferasesPeptide LibraryVirionCapsid ProteinsErb-b2 Receptor Tyrosine Kinaseshexon capsid protein, AdenovirusLuciferasesPeptide Library

Identifiers

PMID21056576
PMCPMC3149894
OpenAlexW2043404405

What OpenQuestion holds

Textmetadata
LicenceTDM
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.