Scientists create artificial genes to determine cellular responses to drugs

Researchers at Boston University’s School of Medicine (BUSM) have developed and implemented new technology. It will make it possible to better understand how human cells communicate with each other, how this communication is disturbed in human diseases, and how this can be corrected pharmacologically. The study is published in the scientific journal Cell.

The technology of scientists consists of a set of “biosensors”. They are artificial genes that can be introduced into cells to communicate in real-time when an important group of signaling molecules is turned on. These signaling molecules, “G-proteins”, are molecular switches in cells. They include a large family of receptor proteins that recognize a very wide range of stimuli, including light, smells, neurotransmitters, and hormones.

This signaling mechanism has been studied for several decades. However, the “new biosensors” are designed to study G-proteins with accuracy that was not possible before.

Scientists call them “spies” – they can tell researchers everything that G-proteins do in real-time, but without interfering with the observed signal transmission process. Moreover, biosensors have an advantage in ease of implementation, which allows scientists to study G-proteins directly in experimental systems that were previously not available.

Researchers have used molecular engineering to create biosensors. They borrowed parts from existing genes, including those that encode fluorescent proteins in jellyfish; also proteins that cause muscles to contract, light-emitting proteins from deep-sea shrimp, and proteins that specifically recognize active G-proteins. Scientists then presented engineered genes that convert biosensors into several different types of cells and studied how they respond to stimulation with natural stimuli — neurotransmitters or clinically used drugs.

According to researchers, more than a third of the FDA-approved U.S. Food and Drug Administration (FDA) medications work on the principle of activating or inhibiting G-protein signaling, including conventional allergy medications, nasal medications, and often prescribed blood pressure medications. In addition, these drugs also include those that are treated for Parkinson’s disease, as well as analgesics, antipsychotics, and opioids.

Scientists believe that these “biosensors” can be useful for discovering and developing new drugs, as well as for a more complete understanding of the principles of action of many existing drugs. Researchers will be able to more easily and accurately identify drugs that are more likely to be successful in clinical trials. Now, many drugs that initially show promise in experimental systems do not ultimately produce clinical results.