Remote Control of Mammalian Cells with Heat-Triggered Gene Switches

This 2018 paper by Ian C. Miller, Gabriel A. Kwong, and colleagues describes a method for precisely controlling gene expression in mammalian T-cells in vivo using remotely applied heat.

Heat-Triggered Gene Switches

The researchers engineered a thermal gene switch using the promoter of the human heat shock protein HSPA6. This switch is inactive at normal body temperature (37°C) but strongly activates gene expression when the temperature is elevated to a narrow window between 40°C and 42°C.

Photothermal Remote Control

To trigger this switch remotely in a living organism, the team used plasmonic gold nanorods. These nanoparticles absorb near-infrared (NIR) laser light and convert it into localized heat (the photothermal effect). By injecting these nanorods alongside the engineered T-cells in mice, they could shine a NIR laser through the skin to heat the local tissue, thereby activating the genetic switch and triggering targeted gene expression with high spatial precision.

Thermal Pulse Trains

A key finding of the study is that delivering the heat in discrete “pulses” (e.g., 10 minutes on, 5 minutes off) rather than continuous heating significantly increased the cells’ thermal tolerance and viability. This allowed the researchers to maintain long-term remote control over the engineered cells over a period of weeks without killing them.

Implications

Alongside optogenetics (see Rapid_blue_light_induction_of_protein_interactions_in_living_cells) and magnetogenetics (see Remote_regulation_of_glucose_homeostasis_in_mice_using_genetically_encoded_nanoparticles), this technology provides another modality for the external, non-invasive control of biological and neurological processes, highlighting the growing intersection of nanotechnology, electromagnetism, and synthetic biology.

See Also