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

被引：13
作者：
Ye, Lupeng [1 ,2 ,3 ,9 ]
Lam, Stanley Z. [1 ,2 ,3 ]
Yang, Luojia [1 ,2 ,3 ,4 ]
Suzuki, Kazushi [1 ,2 ,3 ]
Zou, Yongji [1 ,2 ,3 ]
Lin, Qianqian [1 ,2 ,3 ]
Zhang, Yueqi [1 ,2 ,3 ]
Clark, Paul [1 ,2 ,3 ]
Peng, Lei [1 ,2 ,3 ]
Chen, Sidi [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ]
机构：
[1] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[2] Yale Univ, Syst Biol Inst, West Haven, CT 06516 USA
[3] Yale Univ, Ctr Canc Syst Biol, West Haven, CT 06516 USA
[4] Yale Univ, Mol Cell Biol Genet & Dev Program, New Haven, CT 06520 USA
[5] Yale Univ, Immunobiol Program, New Haven, CT 06520 USA
[6] Yale Univ, Yale Comprehens Canc Ctr, Sch Med, New Haven, CT 06520 USA
[7] Yale Univ, Yale Stem Cell Ctr, Sch Med, New Haven, CT 06520 USA
[8] Yale Univ, Sch Med, Yale Ctr Biomed Data Sci, New Haven, CT 06520 USA
[9] Nanjing Univ, Inst Modern Biol, Nanjing, Peoples R China
来源：
NATURE BIOMEDICAL ENGINEERING | 2024年 / 8卷 / 02期
关键词：
GENE-THERAPY; STEM-CELLS; IN-VITRO; T-CELLS; SAFETY SWITCH; NK CELLS; CAR; INTEGRATION; VECTOR; LANDSCAPE;
D O I：
10.1038/s41551-023-01058-6
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
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. A gene-delivery system relying on a Sleeping Beauty transposase encoded into an mRNA delivered by an adeno-associated virus enhances the stability and efficiency of the integration and expression of a desired transgene in immune cells.
引用
收藏
页码：132 / +
页数：27
相关论文
共 87 条
  • [1] genomation: a toolkit to summarize, annotate and visualize genomic intervals
    Akalin, Altuna
    Franke, Vedran
    Vlahovicek, Kristian
    Mason, Christopher E.
    Schuebeler, Dirk
    [J]. BIOINFORMATICS, 2015, 31 (07) : 1127 - 1129
  • [2] CRISPR off-target analysis in genetically engineered rats and mice
    Anderson, Keith R.
    Haeussler, Maximilian
    Watanabe, Colin
    Janakiraman, Vasantharajan
    Lund, Jessica
    Modrusan, Zora
    Stinson, Jeremy
    Bei, Qixin
    Buechler, Andrew
    Yu, Charles
    Thamminana, Sobha R.
    Tam, Lucinda
    Sowick, Michael-Anne
    Alcantar, Tuija
    O'Neil, Natasha
    Li, Jinjie
    Ta, Linda
    Lima, Lisa
    Roose-Girma, Merone
    Rairdan, Xin
    Durinck, Steffen
    Warming, Soren
    [J]. NATURE METHODS, 2018, 15 (07) : 512 - +
  • [3] THE HUMAN LEUKEMIA-CELL LINE, THP-1 - A MULTIFACETED MODEL FOR THE STUDY OF MONOCYTE-MACROPHAGE DIFFERENTIATION
    AUWERX, J
    [J]. EXPERIENTIA, 1991, 47 (01): : 22 - 31
  • [4] Gene editing for immune cell therapies
    Bailey, Stefanie R.
    Maus, Marcela V.
    [J]. NATURE BIOTECHNOLOGY, 2019, 37 (12) : 1425 - 1434
  • [5] Harnessing a high cargo-capacity transposon for genetic applications in vertebrates
    Balciunas, Darius
    Wangensteen, Kirk J.
    Wilber, Andrew
    Bell, Jason
    Geurts, Aron
    Sivasubbu, Sridhar
    Wang, Xin
    Hackett, Perry B.
    Largaespada, David A.
    McIvor, R. Scott
    Ekker, Stephen C.
    [J]. PLOS GENETICS, 2006, 2 (11): : 1715 - 1724
  • [6] Bushnell B., 2014, LBNL7065E
  • [7] Cameron P, 2017, NAT METHODS, V14, P600, DOI [10.1038/NMETH.4284, 10.1038/nmeth.4284]
  • [8] Transposon-mediated generation of CAR-T cells shows efficient anti B-cell leukemia response after ex vivo expansion
    Chicaybam, Leonardo
    Abdo, Luiza
    Viegas, Mariana
    Codeco Marques, Luisa Vieira
    de Sousa, Priscila
    Batista-Silva, Leonardo Ribeiro
    Alves-Monteiro, Viviane
    Bonecker, Simone
    Monte-Mor, Barbara
    Bonamino, Martin Hernan
    [J]. GENE THERAPY, 2020, 27 (1-2) : 85 - 95
  • [9] CAR T Cells Generated Using Sleeping Beauty Transposon Vectors and Expanded with an EBV-Transformed Lymphoblastoid Cell Line Display Antitumor Activity In Vitro and In Vivo
    Chicaybam, Leonardo
    Abdo, Luiza
    Carneiro, Mayra
    Peixoto, Barbara
    Viegas, Mariana
    de Sousa, Priscila
    Fornazin, Marcia C.
    Spago, Maria C.
    Albertoni Laranjeira, Angelo Brunelli
    de Campos-Lima, Pedro O.
    Nowill, Alexandre
    Carvalho Barros, Luciana Rodrigues
    Bonamino, Martin H.
    [J]. HUMAN GENE THERAPY, 2019, 30 (04) : 511 - 522
  • [10] CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma
    Chu, J.
    Deng, Y.
    Benson, D. M.
    He, S.
    Hughes, T.
    Zhang, J.
    Peng, Y.
    Mao, H.
    Yi, L.
    Ghoshal, K.
    He, X.
    Devine, S. M.
    Zhang, X.
    Caligiuri, M. A.
    Hofmeister, C. C.
    Yu, J.
    [J]. LEUKEMIA, 2014, 28 (04) : 917 - 927
123456789