What Is Chemogenetics?

Chemogenetics is the processes by which macromolecules can be engineered to interact with previously unrecognized small molecules. Chemogenetics as a term was originally coined to describe the observed effects of mutations on chalcone isomerase activity on substrate specificities in the flowers of Dianthus caryophyllus.

This method is very similar to optogenetics however, it uses chemically engineered molecules and ligands instead of light and light-sensitive channels known as Opsins.

In recent research projects, chemogenetics has been widely used to understand the relationship between brain activity and behavior. Prior to chemogenetics, researchers used methods such as transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) to study the relationship between neuronal activity and behavior.

Applications Of Chemogenetics

G-protein coupled receptors and chemogenetics are currently targets for many pharmaceutical companies to cure and alleviate symptoms of diseases that involve all tissues of the body. More specifically, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have been used to explore treatment options for various neurodegenerative and psychological conditions such as Parkinson’s disease, depression, anxiety, and addiction. These aforementioned conditions involve processes that occur within and outside of the nervous system involving neurotransmitters such as GABA and Glutamate.

Chemogenetics has therefore been used in pharmacology to adjust the levels of such neurotransmitters in specific neuron while minimizing the side effects of treatment. To treat and relieve the symptoms of any disease using the DREADDs, these receptors are delivered to the area of interest via viral transduction.

Recently some studies have considered using a new method called retro DREADDs. This method allows specific neuronal pathways to be studied under cellular resolution. Unlike classic DREADDs, this method is usually used in wild type animals, and these receptors are given to the targeted cells via injection of two viral vectors.

Comparison To Optogenetics

Optogenetics and chemogenetics are the more recent and popular methods used to study this relationship. Both of these methods target specific brain circuits and cell population to influence cell activity.

However, they use different procedures to accomplish this task. Optogenetics uses light-sensitive channels and pumps that are virally introduced into neurons. Cells’ activity, having these channels, can then be manipulated by light.

Chemogenetics, on the other hand, uses chemically engineered receptors and exogenous molecules specific for those receptors, to affect the activity of those cells. The engineered macromolecules used to design these receptors include nucleic acid hybrids, kinases, metabolic enzymes, and G-protein coupled receptors (GPCRs) such as DREADDs.

DREADDs are the most common GPCRs used in chemogenetics. These receptors solely get activated by the drug of interest (inert molecule) and influence physiological and neural processes that take place within and outside of the central nervous system.

Chemogenetics has recently been favored over Optogenetics, and it avoids some of the challenges of Optogenetics. Chemogenetics does not require the expensive light equipment, and therefore, is more accessible. The resolution in Optogenetic declines due to light scattering and illuminance declined levels as the distance between the subject and the light source increases.

These factors, therefore, don’t allow for all cells to be affected by light and lead to a lower spatial resolution. Chemogenetics, however, does not require light usage and therefore can achieve a higher spatial resolution.