chemogenetik

Chemogenetics refers to a set of methods that control the activity, signaling, or fate of specific cells by using engineered proteins that respond to externally applied chemical compounds. The approach combines genetic targeting with pharmacology to achieve selective and reversible modulation of cellular function in living organisms, often with a focus on neural circuits.

The core tools are engineered receptors and ion channels that are activated or inhibited by ligands that are otherwise inert in the system. The most widely used are designer receptors exclusively activated by designer drugs (DREADDs), which are modified G protein–coupled receptors that respond to synthetic ligands such as clozapine-N-oxide. Another family includes pharmacologically selective actuator modules (PSAMs) paired with corresponding selective MS ligands (PSEMs). After expression in targeted cells, systemic or local ligand administration induces controlled signaling, typically over minutes to hours, enabling upregulation or suppression of cellular activity.

Applications are prominent in neuroscience, where chemogenetics is used to dissect neural circuits, influence behaviors, and model neurological or psychiatric conditions. It also has potential in other tissues, including the immune system, where cell-type–specific manipulation can reveal functional roles. Chemogenetic approaches are valued for their genetic specificity, reversibility, and flexible temporal control, though they generally offer slower timescales than optogenetics and may face challenges related to ligand delivery, specificity, and off-target effects.

Limitations and considerations include variability in expression, potential systemic effects of ligands, metabolic conversion of compounds to active byproducts, and ethical or translational concerns when moving beyond animal research. Ongoing development aims to broaden toolkits, improve ligand properties, and enhance translational relevance.