Evidence map›Paper›PMID 39910375›Full record

ArticleNature biomedical engineering2025

Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.

Alan Rosales, Leo O Blondel, Joshua Hull, Qimeng Gao, Nihal Aykun, Jennifer L Peek, Alejandra Vargas, Sophia Fergione, Mingqing Song, Matthew H Wilson and 2 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
–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

22 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. 2025 in review.Nature biomedical engineering · 2025
    Article
  15. In vivo base editing reduces liver cysts in autosomal dominant polycystic kidney disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  20. Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    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.

Alan RosalesDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0001-6986-2985
Leo O BlondelDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Joshua HullDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Qimeng GaoDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Nihal AykunDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0001-5435-5016
Jennifer L PeekDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-1239-8752
Alejandra VargasDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Sophia FergioneDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Mingqing SongDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-2462-9351
Matthew H WilsonDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3776-8350
Andrew S BarbasDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-3476-2313
Aravind AsokanDepartment of Biomedical Engineering, Duke University, Durham, NC, USA. aravind.asokan@duke.edu.ORCID http://orcid.org/0000-0001-5563-4877

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
Medical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8M
Genetic engineering of kidney allografts by ex vivo perfusion delivery of adeno-associated viral vectorsU01AI170064 · NIAID · DUKE UNIVERSITY · PI Aravind Asokan, Andrew Serghios Barbas · 2022 to 2026
$2.4M
Evolving High Potency AAV Vectors for Neuromuscular Genome EditingUH3AR075336 · NIAMS · DUKE UNIVERSITY · PI ASOKAN, ARAVIND · 2021 to 2022
$2.0M
Next generation transposon vectors for genome engineeringR01EB033676 · NIBIB · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, MATTHEW H · 2022 to 2025
$2.0M
Proximal Tubule Targeted Gene Therapy for CystinuriaF30DK134046 · NIDDK · VANDERBILT UNIVERSITY · PI PEEK, JENNIFER · 2022 to 2025
$173k
BLRD VA I01 BX004258NHLBI NIH HHS R01 HL089221NIAID NIH HHS U01 AI170064NIAMS NIH HHS UH3 AR075336NIBIB NIH HHS R01 EB033676NIDDK NIH HHS F30 DK134046NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL089221U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U01AI170064U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) UH3AR075336U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB033676U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) F30DK134046
6 · The paper itself

Abstract

The difficulty of delivering genes to the kidney has limited the translation of genetic medicines, particularly for the more than 10% of the global population with chronic kidney disease. Here we show that new variants of adeno-associated viruses (AAVs) displaying robust and widespread transduction in the kidneys of mice, pigs and non-human-primates can be obtained by evolving capsid libraries via cross-species cycling in different kidney models. Specifically, the new variants, AAV.k13 and AAV.k20, were enriched from the libraries following sequential intravenous cycling through mouse and pig kidneys, ex vivo cycling in human organoid cultures, and ex vivo machine perfusion in isolated kidneys from rhesus macaques. The two variants transduced murine kidneys following intravenous administration, with selective tropism for proximal tubules, and led to markedly higher transgene expression than parental AAV9 vectors in proximal tubule epithelial cells within human organoid cultures and in autotransplanted pig kidneys. Following ureteral delivery, AAV.k20 efficiently transduced kidneys in pigs and macaques. The AAV.k13 and AAV.k20 variants are promising vectors for therapeutic gene-transfer applications in kidney diseases and transplantation.

Indexed as

CapsidCapsid ProteinsDependovirusGene Transfer TechniquesKidneyAnimalsGenetic TherapyGenetic VectorsHumansMacaca mulattaMiceOrganoidsSwineTransduction, GeneticCapsid Proteins

Identifiers

PMID39910375
PMCPMC12261118

What OpenQuestion holds

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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.