Evidence map›Paper›PMID 30534580›Full record

ArticleMolecular therapy. Methods & clinical development2019

Codon-Optimization of Wild-Type Adeno-Associated Virus Capsid Sequences Enhances DNA Family Shuffling while Conserving Functionality.

Marti Cabanes-Creus, Samantha L Ginn, Anais K Amaya, Sophia H Y Liao, Adrian Westhaus, Claus V Hallwirth, Patrick Wilmott, Jason Ward, Kimberley L Dilworth, Giorgia Santilli and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Novel AAV variants with improved tropism for human Schwann cells.Molecular therapy. Methods & clinical development · 2024
    Article
  8. Development of CNS tropic AAV1-like variants with reduced liver-targeting following systemic administration in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  9. Codon-optimization in gene therapy: promises, prospects and challenges.Frontiers in bioengineering and biotechnology · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. The intersection of vector biology, gene therapy, and hemophilia.Research and practice in thrombosis and haemostasis · 2021
    Review
  19. Review
  20. 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

16 authors at 6 institutions in 4 countries.

Marti Cabanes-CreusTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Samantha L GinnGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Sydney, NSW 2006, Australia.
Anais K AmayaGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Sydney, NSW 2006, Australia.
Sophia H Y LiaoTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Adrian WesthausTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Claus V HallwirthGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Sydney, NSW 2006, Australia.
Patrick WilmottTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Jason WardTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Kimberley L DilworthVector and Genome Engineering Facility, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Giorgia SantilliGreat Ormond Street Institute of Child Health, University College London, London, UK.
Arkadiusz RybickiVector and Genome Engineering Facility, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Hiroyuki NakaiOregon Health & Science University, Portland, OR 97239, USA.
Adrian J ThrasherGreat Ormond Street Institute of Child Health, University College London, London, UK.
Adrian C FilipTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Sydney, NSW 2006, Australia.
Leszek LisowskiTranslational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
University of Sydney · AUChildren's Medical Research Institute · AUGreat Ormond Street Hospital · GBSydney Children’s Hospitals Network · AUOregon Health & Science University · USUniversity College London · GB

Funding

AAV capsid functions, immune evasion and neuronal targeting in mice and NHPR01NS088399 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI NAKAI, HIROYUKI · 2014 to 2018
$1.7M
NINDS NIH HHS R01 NS088399Wellcome Trust
6 · The paper itself

Abstract

Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human seroreactivity, and increased manufacturability. Selection strategies based on directed evolution rely on the generation of highly variable AAV capsid libraries using methods such as DNA-family shuffling, a technique reliant on stretches of high DNA sequence identity between input parental capsid sequences. This identity dependence for reassembly of shuffled capsids is inherently limiting and results in decreased shuffling efficiency as the phylogenetic distance between parental AAV capsids increases. To overcome this limitation, we have developed a novel codon-optimization algorithm that exploits evolutionarily defined codon usage at each amino acid residue in the parental sequences. This method increases average sequence identity between capsids, while enhancing the probability of retaining capsid functionality, and facilitates incorporation of phylogenetically distant serotypes into the DNA-shuffled libraries. This technology will help accelerate the discovery of an increasingly powerful repertoire of AAV capsid variants for cell-type and disease-specific applications.

Indexed as

AAVcapsidcodon optimizationdirected evolutionDNA shufflinglibrary

Identifiers

PMID30534580
PMCPMC6279885
OpenAlexW2898762562

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.