Evidence map›Paper›PMID 34361120›Full record

ArticleInternational journal of molecular sciences2021

Development of a Bispecific Antibody-Based Platform for Retargeting of Capsid Modified AAV Vectors.

Juliane Kuklik, Stefan Michelfelder, Felix Schiele, Sebastian Kreuz, Thorsten Lamla, Philipp Müller, John E Park

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. 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
0.9field-weighted citation impact, top 23% 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, 17 citations in OpenAlex.

  1. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. 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
  14. Review
  15. Review
  16. 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

7 authors at 1 institution in 1 country.

Juliane KuklikDivision of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Stefan MichelfelderDivision of Research Beyond Borders, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Felix SchieleDivision of Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Sebastian KreuzDivision of Research Beyond Borders, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Thorsten LamlaDivision of Drug Discovery Sciences Biberach, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Philipp MüllerBoehringer Ingelheim Venture Fund GmbH, 55216 Ingelheim am Rhein, Germany.ORCID 0000-0001-9961-4376
John E ParkDivision of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany.
Boehringer Ingelheim (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A major limiting factor for systemically delivered gene therapies is the lack of novel tissue specific AAV (Adeno-associated virus) derived vectors. Bispecific antibodies can be used to redirect AAVs to specific target receptors. Here, we demonstrate that the insertion of a short linear epitope "2E3" derived from human proprotein-convertase subtilisin/kexin type 9 (PCSK9) into different surface loops of the VP capsid proteins can be used for AAV de-targeting from its natural receptor(s), combined with a bispecific antibody-mediated retargeting. We chose to target a set of distinct disease relevant membrane proteins-fibroblast activation protein (FAP), which is upregulated on activated fibroblasts within the tumor stroma and in fibrotic tissues, as well as programmed death-ligand 1 (PD-L1), which is strongly upregulated in many cancers. Upon incubation with a bispecific antibody recognizing the 2E3 epitope and FAP or PD-L1, the bispecific antibody/rAAV complex was able to selectively transduce receptor positive cells. In summary, we developed a novel, rationally designed vector retargeting platform that can target AAVs to a new set of cellular receptors in a modular fashion. This versatile platform may serve as a valuable tool to investigate the role of disease relevant cell types and basis for novel gene therapy approaches.

Indexed as

Antibodies, BispecificCapsidCapsid ProteinsDependovirusEndopeptidasesEpitopesFibroblast Activation Protein AlphaGenetic TherapyGenetic VectorsGene Transfer TechniquesHumansMembrane ProteinsProprotein Convertase 9Transduction, GeneticAntibodies, BispecificCapsid ProteinsEndopeptidasesEpitopesFibroblast Activation Protein AlphaMembrane ProteinsPCSK9 protein, humanProprotein Convertase 9AAVadeno-associated viral vectorsbispecific antibodycapsid modificationFAPPD-L1protein engineeringretargeting

Identifiers

PMID34361120
PMCPMC8347852
OpenAlexW3191744966

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.