Evidence map›Paper›PMID 38627969›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.

Joseph G Skeate, Emily J Pomeroy, Nicholas J Slipek, Bryan J Jones, Bryce J Wick, Jae-Woong Chang, Walker S Lahr, Erin M Stelljes, Xiaobai Patrinostro, Blake Barnes and 14 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

20 citing papers in PubMed, 17 citations in OpenAlex.

  1. Mining and engineering of activeSynthetic and systems biotechnology · 2027
    Article
  2. Article
  3. Article
  4. Article
  5. Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  6. Review
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  14. Article
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  16. Article
  17. Review
  18. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  19. Article
  20. Empowering virus-free CAR immune cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 2 institutions in 1 country.

Joseph G SkeateDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Emily J PomeroyDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Bryan J JonesBio-Techne, Minneapolis, MN 55413, USA.
Bryce J WickDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Jae-Woong ChangDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Erin M StelljesDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Xiaobai PatrinostroBio-Techne, Minneapolis, MN 55413, USA.
Blake BarnesBio-Techne, Minneapolis, MN 55413, USA.
Trevor ZareckiBio-Techne, Minneapolis, MN 55413, USA.
Joshua B KruegerDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Jacob E BridgeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Gabrielle M RobbinsDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Madeline D McCormickDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
John R LeerarBio-Techne, Minneapolis, MN 55413, USA.
Kari T WenzelBio-Techne, Minneapolis, MN 55413, USA.
Kathlyn M HornbergerBio-Techne, Minneapolis, MN 55413, USA.
Kirsti WalkerBio-Techne, Minneapolis, MN 55413, USA.
Dalton SmedleyBio-Techne, Minneapolis, MN 55413, USA.
David A LargaespadaDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Neil OttoBio-Techne, Minneapolis, MN 55413, USA.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: webb0178@umn.edu.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: mori0164@umn.edu.
University of Minnesota · USR&D Systems (United States) · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI SCOTT H KAUFMANN · 2009 to 2026
$37.0M
Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
TRAINING IN HEMOGLOBIN &CELL MEMBRANE RESEARCHT32HL007062 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller, Gregory M Vercellotti · 1985 to 2026
$10.3M
Project 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI ODDE, DAVID J. · 2021 to 2025
$9.4M
TECH CoreU54CA268069 · NCI · UNIVERSITY OF MINNESOTA · PI Kevin William Eliceiri, Paolo Provenzano · 2022 to 2026
$8.2M
SCGE Disease Models Studies Supplement: Evaluation of prime editing for the amelioration of alpha-1-antitrypsin deficiency in murine and porcine models.U24OD026641 · OD · RECOMBINETICS, INC. · PI CARLSON, DANIEL FRED · 2018 to 2022
$4.1M
Activated NK CAR Cells to Cure HIVR01AI161017 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S, SKINNER, PAMELA J · 2021 to 2025
$3.8M
Deconvoluting the Ewing sarcoma genetic program using ancestry-informed human iPSC modelingR37CA276345 · NCI · UNIVERSITY OF MINNESOTA · PI Beau Richard Webber · 2023 to 2026
$2.2M
Engineered B Cells as a Universal Platform for the Treatment of EnzymopathiesR01AI146009 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2020 to 2024
$1.9M
Multiplex Engineered Human Lymphocytes for Therapeutic Protein DeliveryR21AI163731 · NIAID · UNIVERSITY OF MINNESOTA · PI WEBBER, BEAU RICHARD · 2021 to 2022
$426k
Determining the cell of origin in Ewing sarcoma through genomic analysisR21CA237789 · NCI · UNIVERSITY OF MINNESOTA · PI SPECTOR, LOGAN G., WEBBER, BEAU RICHARD · 2020 to 2021
$396k
NCI NIH HHS P01 CA254849NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA136393NCI NIH HHS R21 CA237789NCI NIH HHS R37 CA276345NCI NIH HHS U54 CA232561NCI NIH HHS U54 CA268069NHLBI NIH HHS T32 HL007062NIAID NIH HHS R01 AI146009NIAID NIH HHS R01 AI161017NIAID NIH HHS R21 AI163731NIH HHS F30 OD030021NIH HHS U24 OD026641
6 · The paper itself

Abstract

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure-guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells. Our proof-of-principle TcB-M engineering of CAR-NK and CAR-T cells shows low integrated vector copy number, a safe insertion site profile, robust in vitro function, and improves survival in a Burkitt lymphoma xenograft model in vivo. Overall, TcB-M is a versatile, safe, efficient and open-source option for the rapid manufacture and preclinical testing of primary human immune cell therapies through delivery of multicistronic large cargo via transposition.

Indexed as

Burkitt LymphomaGenetic VectorsImmunotherapy, AdoptiveReceptors, Chimeric AntigenTransposasesAnimalsCell Line, TumorDNA Transposable ElementsHumansKiller Cells, NaturalMiceT-LymphocytesTransgenesXenograft Model Antitumor AssaysDNA Transposable ElementsReceptors, Chimeric AntigenTransposasescellular therapy engineeringchimeric antigen receptorsengineering pipelinehigh-throughput mutant screeningimmunotherapyNK cellsT celltransposons

Identifiers

PMID38627969
PMCPMC11184336
OpenAlexW4394844998

What OpenQuestion holds

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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.