Evidence map›Paper›PMID 40629114›Full record

ArticleGene therapy2025

hafoe: an interactive tool for the analysis of chimeric AAV libraries after random mutagenesis.

Tatevik Jalatyan, Erik Aznauryan, Rokib Hasan, Valeri Vardanyan, Stepan Nersisyan, David B Thompson, Noah Davidsohn, Sanya Thomas, Simon van Haren, Jenny Tam and 3 more

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In one paragraph

Article in Gene therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Distinct YY dinucleotide periodicity in adeno-associated virus DNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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

13 authors.

Tatevik Jalatyan *Armenian Bioinformatics Institute, Yerevan, Armenia. tatevik.jalatyan@abi.am.ORCID 0000-0002-8548-7916
Erik Aznauryan *Wyss Institute, Harvard University, Boston, MA, USA.ORCID 0000-0001-7666-7299
Rokib HasanRejuvenate Bio, San Diego, CA, USA.
Valeri VardanyanKavli Institute for the Physics and Mathematics of the Universe, The University of Tokyo, Tokyo, Japan.
Stepan NersisyanArmenian Bioinformatics Institute, Yerevan, Armenia.ORCID 0000-0002-8830-4679
David B ThompsonWyss Institute, Harvard University, Boston, MA, USA.
Noah DavidsohnRejuvenate Bio, San Diego, CA, USA.
Sanya ThomasHarvard Medical School, Harvard University, Boston, MA, USA.
Simon van HarenHarvard Medical School, Harvard University, Boston, MA, USA.
Jenny TamWyss Institute, Harvard University, Boston, MA, USA.ORCID 0000-0002-3767-7205
Denitsa MilanovaWyss Institute, Harvard University, Boston, MA, USA.
George M ChurchWyss Institute, Harvard University, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID 0000-0003-3535-2076
Lilit NersisyanArmenian Bioinformatics Institute, Yerevan, Armenia. lilit.nersisyan@abi.am.ORCID 0000-0001-8525-420X

Funding

Gates Foundation INV-033391
6 · The paper itself

Abstract

Naturally occurring adeno-associated viruses (AAVs) are an integral part of gene therapy, yet engineering novel AAV variants is necessary to expand targetable tissues and treatable diseases. Directed evolution, particularly through DNA shuffling of the capsid genes of wild-type AAV serotypes, is a widely employed strategy to generate novel chimeric variants with desired properties. Yet, the computational analysis of such chimeric sequences presents challenges. We introduce hafoe, a novel computational tool designed for the exploratory analysis of chimeric AAV libraries, which does not require extensive bioinformatics expertise. hafoe accurately deciphers the serotype composition and enrichment patterns of chimeric AAV variants across different tissues. Validation against synthetic datasets demonstrates that hafoe identifies parental serotype compositions with an accuracy of 96.3% to 97.5%. Additionally, we engineered chimeric AAV capsid libraries and screened novel AAV variants for tropism to human dermal fibroblasts and dendritic cells, as well as canine muscle, and liver tissues. Using hafoe we identified and characterized enriched AAV variants in these tissues for potential use in gene therapy and vaccine development. Overall, hafoe can provide valuable insights that may further support the rational design of AAV vectors based on parental serotype and sequence preferences of the capsid genes in target tissues.

Indexed as

Computational BiologyDependovirusAnimalsCapsid ProteinsDogsGene LibraryGenetic TherapyGenetic VectorsHumansMutagenesisSerogroupCapsid Proteins

Identifiers

PMID40629114
PMCPMC12518119

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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.