Mage transposon: a novel gene delivery system for mammalian cells

Author:

Tian Jinghan1,Tong Doudou1,Li Zhendong2,Wang Erqiang1,Yu Yifei2,Lv Hangya2,Hu Zhendan2,Sun Fang2,Wang Guoping1,He Min2,Xia Tian13ORCID

Affiliation:

1. Institute of Pathology, Department of Pathology, School of Basic Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei 430030 , China

2. Elongevity Inc , Wuhan , Hubei 430000 , China

3. School of Artificial Intelligence and Automation, Huazhong University of Science and Technology , Wuhan , Hubei 430074 , China

Abstract

Abstract Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Reference84 articles.

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