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A non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice

Author

Listed:
  • Jiali Wu

    (East China Normal University)

  • Meiyan Wang

    (East China Normal University)

  • Xueping Yang

    (East China Normal University)

  • Chengwei Yi

    (East China Normal University)

  • Jian Jiang

    (East China Normal University)

  • Yuanhuan Yu

    (East China Normal University)

  • Haifeng Ye

    (East China Normal University)

Abstract

The Cre-loxP recombination system is a powerful tool for genetic manipulation. However, there are widely recognized limitations with chemically inducible Cre-loxP systems, and the UV and blue-light induced systems have phototoxicity and minimal capacity for deep tissue penetration. Here, we develop a far-red light-induced split Cre-loxP system (FISC system) based on a bacteriophytochrome optogenetic system and split-Cre recombinase, enabling optogenetical regulation of genome engineering in vivo solely by utilizing a far-red light (FRL). The FISC system exhibits low background and no detectable photocytotoxicity, while offering efficient FRL-induced DNA recombination. Our in vivo studies showcase the strong organ-penetration capacity of FISC system, markedly outperforming two blue-light-based Cre systems for recombination induction in the liver. Demonstrating its strong clinical relevance, we successfully deploy a FISC system using adeno-associated virus (AAV) delivery. Thus, the FISC system expands the optogenetic toolbox for DNA recombination to achieve spatiotemporally controlled, non-invasive genome engineering in living systems.

Suggested Citation

  • Jiali Wu & Meiyan Wang & Xueping Yang & Chengwei Yi & Jian Jiang & Yuanhuan Yu & Haifeng Ye, 2020. "A non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17530-9
    DOI: 10.1038/s41467-020-17530-9
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    Cited by:

    1. Charlotte Cautereels & Jolien Smets & Peter Bircham & Dries De Ruysscher & Anna Zimmermann & Peter De Rijk & Jan Steensels & Anton Gorkovskiy & Joleen Masschelein & Kevin J. Verstrepen, 2024. "Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Charlotte Cautereels & Jolien Smets & Jonas De Saeger & Lloyd Cool & Yanmei Zhu & Anna Zimmermann & Jan Steensels & Anton Gorkovskiy & Thomas B. Jacobs & Kevin J. Verstrepen, 2024. "Orthogonal LoxPsym sites allow multiplexed site-specific recombination in prokaryotic and eukaryotic hosts," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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