Imagine being able to control genetic expression by flipping a light switch.
Researchers at North Carolina
are using light-activated molecules to turn gene expression on and off. Their
method enables greater precision when studying gene function, and could lead to
targeted therapies for diseases like cancer.
Triplex-forming oligonucleotides (TFOs) are commonly used molecules that can
prevent gene transcription by binding to double-stranded DNA. NC State chemist Alex
Deiters, PhD, wanted to find a way to more precisely control TFOs, and by
extension, the transcription of certain genes. So Deiters attached a
light-activated “cage” to a TFO. When exposed to ultraviolet (UV) light, the
cage is removed, and the TFO is free to bind with DNA, inhibiting transcription
of the gene of interest.
“In the absence of light, transcription activity is 100%,” says Deiters. “When we turn on the light, we can take it down to about 25%, which is a
significant reduction in gene expression.”
Additionally, Deiters fine-tuned the process by attaching a caged inhibitor
strand to the TFO. In the absence of UV light, the TFO behaves normally,
binding to DNA and preventing gene expression. However, when exposed to UV
light, the caged inhibitor activates and stops the TFO from binding with DNA,
turning gene transcription on.
“We’ve created a tool that allows for the light-activation of genetic
transcription,” Deiters says. “By giving researchers greater temporal and
spatial control over gene expression, we’ve expanded their ability to study the
behavior of particular genes in whichever environment they choose.”
The research appears online in ACS
Source: North Carolina State University