Evidence map›Paper›PMID 38027057›Full record

ArticleMolecular therapy. Methods & clinical development2023

Multiparametric domain insertional profiling of adeno-associated virus VP1.

Mareike D Hoffmann, Alina C Zdechlik, Yungui He, David Nedrud, George Aslanidi, Wendy Gordon, Daniel Schmidt

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  8. Review
  9. Article
  10. Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024
    Review
  11. Protein Carrier AAV.bioRxiv : the preprint server for biology · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Mareike D HoffmannDepartment of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA.
Alina C ZdechlikDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Yungui HeDepartment of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA.
David NedrudDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
George AslanidiThe Hormel Institute, Austin, MN 55912, USA.
Wendy GordonDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Daniel SchmidtDepartment of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA.
University of Minnesota · USHormel (United States) · US

Funding

Viral Innovation CoreP30DA048742 · NIDA · UNIVERSITY OF MINNESOTA · PI Mark John Thomas · 2020 to 2026
$19.0M
Mechanism and modulation of Amyloid Precursor Protein proteolysisR35GM119483 · NIGMS · UNIVERSITY OF MINNESOTA · PI WENDY RYAN GORDON · 2016 to 2026
$4.6M
Viral vector technology for cell type specific gene deliveryR01GM141152 · NIGMS · UNIVERSITY OF MINNESOTA · PI SCHMIDT, DANIEL · 2022 to 2025
$1.5M
Engineered viral tropism for cell-type specific manipulation of neuronal circuitsU01MH109038 · NIMH · UNIVERSITY OF MINNESOTA · PI SCHMIDT, DANIEL, THOMAS, MARK JOHN · 2015 to 2017
$1.1M
NIDA NIH HHS P30 DA048742NIGMS NIH HHS R01 GM141152NIGMS NIH HHS R35 GM119483
6 · The paper itself

Abstract

Several evolved properties of adeno-associated virus (AAV), such as broad tropism and immunogenicity in humans, are barriers to AAV-based gene therapy. Most efforts to re-engineer these properties have focused on variable regions near AAV's 3-fold protrusions and capsid protein termini. To comprehensively survey AAV capsids for engineerable hotspots, we determined multiple AAV fitness phenotypes upon insertion of six structured protein domains into the entire AAV-DJ capsid protein VP1. This is the largest and most comprehensive AAV domain insertion dataset to date. Our data revealed a surprising robustness of AAV capsids to accommodate large domain insertions. Insertion permissibility depended strongly on insertion position, domain type, and measured fitness phenotype, which clustered into contiguous structural units that we could link to distinct roles in AAV assembly, stability, and infectivity. We also identified engineerable hotspots of AAV that facilitate the covalent attachment of binding scaffolds, which may represent an alternative approach to re-direct AAV tropism.

Indexed as

adeno-associated viruscapsid assemblycapsid engineeringdomain insertional profilinggene therapyHUH tags

Identifiers

PMID38027057
PMCPMC10661864
OpenAlexW4387956086

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.