Evidence map›Paper›PMID 39498467›Full record

ArticleMolecular therapy. Methods & clinical development2024

AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.

Suzanne Scott, Adrian Westhaus, Deborah Nazareth, Marti Cabanes-Creus, Renina Gale Navarro, Deborah Chandra, Erhua Zhu, Aravind Venkateswaran, Ian E Alexander, Denis C Bauer and 2 more

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In one paragraph

Article in Molecular therapy. Methods & clinical development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

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4 · The record

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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.

Suzanne ScottTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Adrian WesthausTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Deborah NazarethTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Marti Cabanes-CreusTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Renina Gale NavarroTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Deborah ChandraTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.
Erhua ZhuGene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Aravind VenkateswaranAustralian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Westmead, NSW 2145, Australia.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Denis C BauerAustralian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Westmead, NSW 2145, Australia.
Laurence O W WilsonAustralian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Westmead, NSW 2145, Australia.
Leszek LisowskiTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene therapies using recombinant adeno-associated virus (AAV) vectors have demonstrated considerable clinical success in the treatment of genetic disorders. Improved vectors with favorable tropism profiles, decreased immunogenicity, and enhanced manufacturability are poised to further improve the state of gene therapies. Such vectors can be identified through directed evolution, a process of subjecting a diverse capsid library to a selection pressure to identify individual variants with a desired trait. Currently, libraries that involve changes distributed throughout the AAV capsid coding region, such as DNA family shuffled libraries, are largely characterized using low-throughput Sanger sequencing of individual clones. However, improvements in long-read sequencing technologies have increased their applicability to capsid libraries and evaluation of the selection process. Here, we explore the application of Oxford Nanopore Technologies refined by a concatemeric consensus method for initial library characterization and monitoring selection of a shuffled AAV capsid library. Furthermore, we present AAVolve, a bioinformatic pipeline for processing long-read data from AAV-directed evolution experiments. Our approach allows high-throughput characterization of AAV capsids in a streamlined manner, facilitating deeper insights into library composition through multiple rounds of selection, and generalization through training of machine learning models.

Indexed as

AAV vectorcapsid engineeringdirected evolutionDNA family shufflinggene therapyOxford Nanopore Technologiesrolling circle amplification to concatemeric consensus

Identifiers

PMID39498467
PMCPMC11532298

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LicenceCC BY-NC-ND
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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.