Evidence map›Paper›PMID 39245720›Full record

ArticleNature communications2024

Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.

Timothy F Shay, Seongmin Jang, Tyler J Brittain, Xinhong Chen, Beth Walker, Claire Tebbutt, Yujie Fan, Damien A Wolfe, Cynthia M Arokiaraj, Erin E Sullivan and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Article
  2. Article
  3. Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  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

16 authors.

Timothy F Shay *Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. tshay@caltech.edu.ORCID 0000-0001-6591-3271
Seongmin Jang *Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID 0000-0002-9822-6790
Tyler J Brittain *Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID 0000-0001-6411-999X
Xinhong Chen *Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Beth WalkerCharles River Laboratories, High Peak Business Park, Buxton Road, Chinley, SK23 6FJ, UK.
Claire TebbuttCharles River Laboratories, High Peak Business Park, Buxton Road, Chinley, SK23 6FJ, UK.
Yujie FanDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Damien A WolfeDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Cynthia M ArokiarajDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID 0000-0003-3201-9868
Erin E SullivanDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Xiaozhe DingDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Ting-Yu WangDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Yaping LeiDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Miguel R ChuapocoDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Tsui-Fen ChouDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.ORCID 0000-0003-2410-2186
Viviana GradinaruDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. viviana@caltech.edu.ORCID 0000-0001-5868-348X

Funding

Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across SpeciesUF1MH128336 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI FOX, ANDREW S, GRADINARU, VIVIANA · 2021 to 2021
$6.1M
Circuit-Specific Delivery of Large Cargo Across the Nervous Systems of Adult Mammals and Embryos via Novel Engineered Systemic VectorsDP1NS111369 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2023
$5.9M
Genetically encoded indicators for large-scale sensing of neuromodulatory signaling in behaving animalsU01NS103522 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI NIMMERJAHN, AXEL, TIAN, LIN · 2017 to 2019
$2.9M
NIMH NIH HHS UF1 MH128336NINDS NIH HHS DP1 NS111369NINDS NIH HHS U01 NS103522U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) UF1MH128336U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) DP1NS111369
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are foundational gene delivery tools for basic science and clinical therapeutics. However, lack of mechanistic insight, especially for engineered vectors created by directed evolution, can hamper their application. Here, we adapt an unbiased human cell microarray platform to determine the extracellular and cell surface interactomes of natural and engineered AAVs. We identify a naturally-evolved and serotype-specific interaction between the AAV9 capsid and human interleukin 3 (IL3), with possible roles in host immune modulation, as well as lab-evolved low-density lipoprotein receptor-related protein 6 (LRP6) interactions specific to engineered capsids with enhanced blood-brain barrier crossing in non-human primates after intravenous administration. The unbiased cell microarray screening approach also allows us to identify off-target tissue binding interactions of engineered brain-enriched AAV capsids that may inform vectors' peripheral organ tropism and side effects. Our cryo-electron tomography and AlphaFold modeling of capsid-interactor complexes reveal LRP6 and IL3 binding sites. These results allow confident application of engineered AAVs in diverse organisms and unlock future target-informed engineering of improved viral and non-viral vectors for non-invasive therapeutic delivery to the brain.

Indexed as

Blood-Brain BarrierDependovirusInterleukin-3Low Density Lipoprotein Receptor-Related Protein-6TranscytosisAnimalsBrainCapsidCapsid ProteinsGenetic VectorsHEK293 CellsHumansProtein BindingCapsid ProteinsInterleukin-3Low Density Lipoprotein Receptor-Related Protein-6LRP6 protein, human

Identifiers

PMID39245720
PMCPMC11381518

What OpenQuestion holds

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Registered trials

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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.