Researchers unveil a powerful new gene-switch tool

Good news! Using a relatively nontoxic poison exon! 😊

"Investigators ... have developed a versatile and nontoxic technology for controlling the activity of any gene in a cell. Such “gene-switch” tools allow scientists to turn a target gene on or off to study how it works, model diseases and design new therapies.

The tool potentially could be adopted throughout biomedical research, including in the development of gene therapies. 

The new tool, called Cyclone (acyclovir-controlled poison exon) ... It was inspired by a natural feature of some genes, a DNA segment called a “poison exon,” which under certain conditions can block the gene from being translated into a protein.

To make Cyclone, the researchers engineered a poison exon that can be inserted into any target gene to suppress its activity. When the researchers are ready to turn up gene activity, a drug that binds to the poison exon is introduced and activity resumes. Unlike existing popular gene-switch tools, Cyclone uses a relatively nontoxic molecule, the antiviral drug acyclovir, to switch on the target gene. ..."

From the abstract:

"The ability to precisely control gene expression using small-molecule drugs is a valuable tool in research and has important therapeutic potential. However, existing systems are often limited by the toxicity of the drugs and the need to alter gene sequences or endogenous regulatory elements.

Here, we introduce Cyclone (acyclovir-controlled poison exon), an acyclovir-controlled poison exon cassette that can be used for small-molecule control of both transgene and endogenous gene expression.

Cyclone is a portable ‘intron–poison exon–intron’ element that can be inserted into nearly any gene and is completely removed upon acyclovir treatment, leaving the native transcript intact.

Cyclone offers tunable, reversible gene expression with nearly undetectable background and a ~295-fold activation.

We also present Pac-Cyclone, a cassette that simplifies the generation of cell lines with acyclovir-controlled endogenous gene expression.

Finally, we demonstrate the programmability of Cyclone, underscoring its potential for developing diverse genetic circuits controlled by various ligands."

Researchers unveil a powerful new gene-switch tool | Cornell Chronicle

Versatile gene-switch tool uses non-toxic molecule for safer research

A portable poison exon for small-molecule control of mammalian gene expression (no public access)

Endogenous gene regulation by Pac-Cyclone