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Engineering

Non-invasive far-red light based bacteriophytochrome optogenetic system for non-invasive genome engineering

By 9th November 2020No Comments

The following study was conducted by Scientists from Synthetic Biology and Biomedical Engineering Laboratory, Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Study is published in Nature Communications Journal as detailed below.

Nature Communications; Volume 11, Article Number: 3708; (2020)

A Non-invasive Far-Red Light-Induced Split-Cre Recombinase System for Controllable Genome Engineering in Mice

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.

Source:

Nature Communications

URL: https://www.nature.com/articles/s41467-020-17530-9

Citation:

Wu, J., M. Wang, et al. (2020). “A non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice.” Nature Communications 11(1): 3708.