Magnetogenetics: Tools for Noninvasive Neuromodulation with Cellular Resolution

Abstract

Magnetogenetics is emerging as a promising tool to control neuronal activity and overcome the limitations of chemogenetics and optogenetics. While chemogenetics is restricted in temporal resolution, optogenetics is invasive and limited in penetration depth. Magnetogenetics addresses these challenges by offering a noninvasive approach that enables wireless and on-demand control of neuronal activity. Magnetogenetics uses synthetic magnetic nanoparticles or the protein ferritin as transducers to convert magnetic fields into thermal, mechanical, or biochemical signals that can activate ion channels and proteins sensitive to these stimuli. To achieve cellular resolution, the neurons of interest are genetically targeted by the expression of diverse ion channels that confer sensitivity to magnetic stimulation or by targeting transducers to ion channels via linkers such as antibodies and other binding domains. Neuroscientists have used magnetogenetics to drive calcium-dependent gene expression, to excite or inhibit neurons, and to modulate behavior in animal models, as discussed in this review. The efficacy of these methods has been met with skepticism, and the fundamental mechanisms have been unclear. However, several studies have demonstrated the effectiveness of magnetogenetics and uncovered the underlying mechanisms. While improvements are still needed for magnetogenetics to become a routine technique to control neuronal activity, there is tremendous potential for both technical innovation and applications. This review discusses the current approaches from their development and limitations to their applications across research fields, particularly neuroscience.