# Magneto-Photonic Gene Circuit for Minimally Invasive Control of Gene Expression in Mammalian Cells

## TL;DR

This paper introduces a new gene circuit that uses bioluminescence and magnetic fields to control gene expression in mammalian cells without external light.

## Contribution

A magneto-photonic gene circuit combining bioluminescence and magnetic sensitivity for non-invasive gene control.

## Key findings

- A luminescent enzyme was used to generate light inside cells for optogenetic control.
- A magneto-sensitive protein enabled enzyme reconstitution via a 50 mT magnetic stimulus.
- The system allows gene regulation without external light sources.

## Abstract

Precise control of
gene expression is one of the fundamental goals
of synthetic biology. Whether the objective is to modify endogenous
cellular function or induce the expression of molecules for diagnostic
and therapeutic purposes, gene regulation remains a key aspect of
biological systems. Over time, advances in protein engineering and
molecular biology have led to the creation of gene circuits capable
of inducing the expression of specific proteins in response to external
stimulus such as light. These optogenetic, or light-activated circuits
hold significant potential for gene therapy as a tool for regulating
the expression of therapeutic genes within cells. However, the applications
of optogenetic systems can be limited by the lack of efficient ways
to deliver light into cells or tissue. Our approach to address this
challenge is to harness the power of bioluminescence to produce light
directly inside cells using a luminescent enzyme. Combined with a
photosensitive transcription factor, we report the development of
a genetically encoded optogenetic circuit for the control of gene
expression. Furthermore, we utilized a magneto-sensitive protein to
engineer a split-protein version of this luminescent enzyme, where
its reconstitution is driven by a 50 mT magnetic stimulus. Thus, resulting
in a gene circuit activated by a combination of light and magnetic
stimulus. We expect this work to advance the implementation of light-controlled
systems without the need of external light sources, as well as serve
as a basis for the development of future magneto-sensitive tools.