Evidence map›Paper›PMID 37430157›Full record

ArticleNature biomedical engineering2024

AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells.

Lupeng Ye, Stanley Z Lam, Luojia Yang, Kazushi Suzuki, Yongji Zou, Qianqian Lin, Yueqi Zhang, Paul Clark, Lei Peng, Sidi Chen

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
8.8field-weighted citation impact, top 2% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Review
  3. Engineering Immune Cell to Counteract Aging and Aging-Associated Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Auto-expansion ofMolecular therapy. Methods & clinical development · 2024
    Article
  13. Review
  14. Review
  15. Review
  16. Massively parallelbioRxiv : the preprint server for biology · 2023
    Article
  17. 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

10 authors at 2 institutions in 2 countries.

Lupeng YeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0003-3901-6598
Stanley Z LamDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Luojia YangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Kazushi SuzukiDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yongji ZouDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Qianqian LinDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yueqi ZhangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Paul ClarkDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Lei PengDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Sidi ChenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. sidi.chen@yale.edu.ORCID 0000-0002-3819-5005
Yale University · USYale Cancer Center · US

Funding

(PQ4) Novel tools for in vivo study of genetic interactions in cancer progressionR01CA231112 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2022
$3.0M
High-throughput in vivo genetics for immunotherapy target discoveryDP2CA238295 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2018
$2.5M
New approaches for single cell tagging, editing and profiling of glial cells in vivoRF1DA048811 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HONG, WEIZHE · 2019 to 2019
$2.4M
Rapidly scalable platforms for direct in vivo screening of functional drivers in lethal cancersR33CA225498 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2019 to 2021
$1.2M
NCI NIH HHS DP2 CA238295NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NIDA NIH HHS RF1 DA048811U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP2CA238295U.S. Department of Health & Human Services | National Institutes of Health (NIH) R33CA225498
6 · The paper itself

Abstract

Engineering cells for adoptive therapy requires overcoming limitations in cell viability and, in the efficiency of transgene delivery, the duration of transgene expression and the stability of genomic integration. Here we report a gene-delivery system consisting of a Sleeping Beauty (SB) transposase encoded into a messenger RNA delivered by an adeno-associated virus (AAV) encoding an SB transposon that includes the desired transgene, for mediating the permanent integration of the transgene. Compared with lentiviral vectors and with the electroporation of plasmids of transposon DNA or minicircle DNA, the gene-delivery system, which we named MAJESTIC (for 'mRNA AAV-SB joint engineering of stable therapeutic immune cells'), offers prolonged transgene expression, as well as higher transgene expression, therapeutic-cell yield and cell viability. MAJESTIC can deliver chimeric antigen receptors (CARs) into T cells (which we show lead to strong anti-tumour activity in vivo) and also transduce natural killer cells, myeloid cells and induced pluripotent stem cells with bi-specific CARs, kill-switch CARs and synthetic T-cell receptors.

Indexed as

DependovirusTransposasesDNA Transposable ElementsGene Transfer TechniquesRNA, MessengerDNA Transposable ElementsRNA, MessengerTransposases

Identifiers

PMID37430157
PMCPMC11320892
OpenAlexW4383814913

What OpenQuestion holds

Textmetadata
LicenceTDM
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.