Evidence map›Paper›PMID 37992599›Full record

ArticleBiomaterials2023

AAV vectors displaying bispecific DARPins enable dual-control targeted gene delivery.

Samuel A Theuerkauf, Elena Herrera-Carrillo, Fabian John, Luca J Zinser, Mariano A Molina, Vanessa Riechert, Frederic B Thalheimer, Kathleen Börner, Dirk Grimm, Petr Chlanda and 2 more

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. An Expanded Toolbox for Versatile Chemical Editing of Adeno-Associated Virus.Angewandte Chemie (International ed. in English) · 2026
    Article
  8. In vivo chimeric antigen receptor (CAR)-T cell therapy.Nature reviews. Drug discovery · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. The rise of cochlear gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  17. Review
  18. Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024
    Review
  19. T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    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

12 authors at 4 institutions in 2 countries.

Samuel A TheuerkaufGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
Elena Herrera-CarrilloUniversity of Amsterdam, Amsterdam, Netherlands.
Fabian JohnGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany; Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.
Luca J ZinserGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
Mariano A MolinaUniversity of Amsterdam, Amsterdam, Netherlands.
Vanessa RiechertGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
Frederic B ThalheimerGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany; Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.
Kathleen BörnerDepartment of Infectious Diseases/Virology, Heidelberg University Hospital, Heidelberg, Germany; BioQuant, Heidelberg University, Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg, Germany.
Dirk GrimmBioQuant, Heidelberg University, Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg, Germany; Department of Infectious Diseases/Virology, Section Viral Vector Technologies, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Heidelberg, Germany.
Petr ChlandaDepartment of Infectious Diseases/Virology, Heidelberg University Hospital, Heidelberg, Germany; BioQuant, Heidelberg University, Heidelberg, Germany; Schaller Research Groups, Heidelberg University, Heidelberg, Germany.
Ben BerkhoutUniversity of Amsterdam, Amsterdam, Netherlands.
Christian J BuchholzGene Therapy and Molecular Biotechnology, Paul-Ehrlich-Institut, Langen, Germany; Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany. Electronic address: christian.buchholz@pei.de.
Amsterdam University of the Arts · NLGoethe University Frankfurt · DEHeidelberg University · DEPaul Ehrlich Institut · DE

Funding

Disabling the replication-competent HIV provirus in the reservoir by combined CRISPR-Cas actionR01AI145045 · NIAID · ACADEMICAL MEDICAL CENTER · PI BERKHOUT, BENJAMIN · 2019 to 2023
$2.6M
NIAID NIH HHS R01 AI145045
6 · The paper itself

Abstract

Precise delivery of genes to therapy-relevant cells is crucial for in vivo gene therapy. Receptor-targeting as prime strategy for this purpose is limited to cell types defined by a single cell-surface marker. Many target cells are characterized by combinations of more than one marker, such as the HIV reservoir cells. Here, we explored the tropism of adeno-associated viral vectors (AAV2) displaying designed ankyrin repeat proteins (DARPins) mono- and bispecific for CD4 and CD32a. Cryo-electron tomography revealed an unaltered capsid structure in the presence of DARPins. Surprisingly, bispecific AAVs transduced CD4/CD32a double-positive cells at much higher efficiencies than single-positive cells, even if present in low amounts in cell mixtures or human blood. This preference was confirmed when vector particles were systemically administered into mice. Cell trafficking studies revealed an increased cell entry rate for bispecific over monospecific AAVs. When equipped with an HIV genome-targeting CRISPR/Cas cassette, the vectors prevented HIV replication in T cell cultures. The data provide proof-of-concept for high-precision gene delivery through tandem-binding regions on AAV. Reminiscent of biological products following Boolean logic AND gating, the data suggest a new option for receptor-targeted vectors to improve the specificity and safety of in vivo gene therapy.

Indexed as

Designed Ankyrin Repeat ProteinsHIV InfectionsAnimalsDependovirusGenetic TherapyGenetic VectorsHumansMiceTransduction, GeneticDesigned Ankyrin Repeat ProteinsCRISPR-CasDART-AAVDesigned ankyrin repeat proteinFcγRIIAHIV reservoirReceptor-targeting

Identifiers

PMID37992599
PMCPMC10721713
OpenAlexW4388736284

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.