Researchers have reported a universal switching element that can precisely control gene replacement or gene editing after exposure to small molecules. This small molecule inducer is currently used in humans, and it is an oral biological agent when given to animals or humans, and can reach peripheral tissues and brain. In addition, the switch system called Xon by researchers does not need any co-expression of regulatory proteins.
By using Xon, the researchers showed that the translation of elements required by gene replacement or gene editing machine occurred after a single oral administration of inducer, and the robustness of expression could be controlled by drug dosage, protein stability and re-administration. The time control ability of protein expression provided by Xon can be applied to cell biology and animal research. In addition, because of the oral bioavailability and safety of the drugs used, Xon switch system provides an unprecedented opportunity to improve and adjust the application of gene therapy in human beings.
According to reports, so far, gene therapy relies on complex constructs and cannot be finely controlled.
Attachment: English original
Title: Regulated control of gene therapies by drug-induced splicing
Author: Monteys, Alex Mas, Hundley, Amiel A., Ranum, Paul T., Tecedor, Luis, Muehlmatt, Amy, Lim, Euyn, Lukashev, Dmitriy, Sivasankaran, Rajeev, Davidson, Beverly L.
Issue&Volume: 2021-07-28
Abstract: So far, gene therapies have relied on complex constructs that cannot be finely controlled1, 2. Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The s mall-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain. Moreover, the switch system, which we denote Xon, does not require the co-expression of any regulatory proteins. Using Xon, the translation of the desired elements for controlled gene replacement or gene editing machinery occurs after a single oral dose of the inducer, and the robustness of expression can be controlled by the drug dose, protein stability and redosing. The ability of Xon to provide temporal control of protein expression can be adapted for cell-biology applications and animal studies. Additionally, owing to the oral bioavailability and safety of the drugs used, the Xon switch system provides an unprecedented opportunity to refine and tailor the application of gene therapies in humans. A switch system is devel oped to control the expression of therapeutic genes, involving the administration of a small-molecule drug to induce splicing-mediated control of mRNA translation.