Chemogenetics a robust approach to pharmacology and gene therapy

Chemogenetics of cell surface receptors: beyond genetic and pharmacological approaches

“…Although chemogenetics have not been applied in human therapeutics or clinical trials, some studies have proceeded in this direction. 11,167 A major concern in clinical use is applicability of designer chemicals to human. In this point, as described in Section 2, olanzapine, a clinically approved antipsychotic drug as a DREADD ligand 42 and varenicline, an approved anti-smoking drug for PSAM/PSEM, would be potential candidates.…”

“…This approach is known as orthogonal chemical genetics, allele-specific chemical genetics, or 1). [9][10][11] We use ''chemogenetics'' in this review, because this terminology is widely used for expression as a complementary method against optogenetics to manipulate cell surface receptors. [12][13][14] In an early study of chemogenetics, Hwang et al reported alteration of nucleotide specificity of E. coli elongation factor Tu (EF-Tu), a GTP regulatory protein, by site-directed mutagenesis.…”

Chemogenetic Approaches to Explore the Functions of Free Fatty Acid Receptor 2

“…The concept of altering the orthosteric binding pocket of a GPCR by mutation to greatly reduce or eliminate the potency of binding of the endogenous agonist(s) whilst, in parallel, generating potency for a distinct agonist has been most effectively developed and demonstrated for members of the group of muscarinic acetylcholine receptors [46][47][48][49].…”

Optogenetic Interrogation of Circuits Following Neurotrauma

“…Recent channelrhodopsin variants can drive firing rates up to several hundred hertz (Mager et al, 2018 ), or be used noninvasively for deep (up to 7 mm) targets (Chen R. et al, 2021 ). If long-term (minutes to hours) modulation is desired, G-protein-coupled receptor-based opsins (opto-XRs), step function opsins, or chemogenetic actuators are more appropriate (Eickelbeck et al, 2019 ; Keifer et al, 2020 ). Conveniently, many opsin constructs are packaged with linked fluorescent proteins or tags that, when bound to the plasma membrane along with the opsin, enable robust anatomical tracing even of narrow, regenerating axons.…”