Evidence map›Paper›PMID 39673125›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.

Adrian Westhaus, Elena Barba-Sarasua, Yuyan Chen, Kenneth Hsu, Suzanne Scott, Maddison Knight, Florencia Haase, Santiago Mesa Mora, Benjamin C Houghton, Ramon Roca-Pinilla and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

15 authors.

Adrian WesthausTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.
Elena Barba-SarasuaTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Yuyan ChenChildren's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Kenneth HsuChildren's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Suzanne ScottTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW, Australia.
Maddison KnightTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Florencia HaaseTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Santiago Mesa MoraTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Benjamin C HoughtonInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.
Ramon Roca-PinillaTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Predrag KalajdzicVector and Genome Engineering Facility, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Geraldine O'NeillChildren's Cancer Research Unit, Kids Research, The Children's Hospital at Westmead, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Adrian J ThrasherInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.
Giorgia SantilliInfection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College, London, UK.
Leszek LisowskiTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Australian Genome Therapeutics Centre, Children's Medical Research Institute and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine - National Research Institute, Warsaw, Poland. Electronic address: llisowski@cmri.org.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate the CAR into the T cell receptor alpha constant (TRAC) locus to take advantage of the endogenous promoter and regulatory elements for CAR expression. This method used adeno-associated viral (AAV) vectors based on AAV6 to deliver the donor template encoding the CAR construct. Since the original publication, improvements have been made to this targeted CAR integration technique; however, none of those techniques focused on improving the AAV vector used to deliver the therapeutic cargo. The herein presented study developed a novel AAV capsid directed evolution platform that allows for specifically selecting for novel AAV capsid variants that enable more efficient targeted gene editing-mediated CAR construct integration into the TRAC locus in primary T cells. Using this new platform, we selected several novel AAVs that enable more efficient editing in T cells than AAV6. Two novel capsids, AAV-T1 and AAV-T2, were able to mediate 5-fold improvement for on-target knockin, which resulted in 5-fold reduction of the vector dose to produce highly cytolytic T cells against a brain tumor cell line.

Indexed as

CapsidCapsid ProteinsDependovirusDirected Molecular EvolutionGenetic VectorsReceptors, Chimeric AntigenGene EditingHumansImmunotherapy, AdoptiveT-LymphocytesCapsid ProteinsReceptors, Chimeric AntigenAAVcancercancer gene therapyCAR-Tcell therapydirected evolutiongene therapyhigh-grade gliomasynthetic biologyT-cell engineering

Identifiers

PMID39673125
PMCPMC12172172

What Socratic 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 Socratic graph.