4 October 2012

Gene therapy gets the blue light

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U.S. researchers have developed a system, triggered by blue light, that can seek out and turn on or off any desired gene, which could be useful for research in biotechnology and in medicine.
Gene therapy gets blue light

To demonstrate the spatial control of the system, the researchers could create patterns, including an array of spots or a smiley face. They illuminated the human cell culture through a photomask of with the smiley face.
Scale bar = 2 mm Credit: Charles Gersbach/JACS

SYDNEY: U.S. researchers have developed a system, triggered by blue light, that can seek out and turn on or off any desired gene, which could be useful for research in biotechnology and in medicine.

This is the first time specific sections of DNA have been turned on and off. The researchers could control where and when a gene was turned on, and how quickly this happened. They also report tuning the level of gene expression using the intensity of the light in their paper published in the Journal of the American Chemical Society.

“We can control where a gene turns on within a tissue, and therefore have control over where, when, and what type of tissue develops,” said biomedical engineer Charles Gersbach at Duke University in Durham, North Carolina, who co-authored the paper.

Gene regulation or tissue reconstruction

“Our work focuses on using molecular and genetic engineering to control cell behavior, ultimately to regenerate diseased or damaged tissues and treat genetic disorders,” he said.

The system, called called LITEZ (light-inducible transcription using engineered zinc finger proteins), operates under blue light, which shifts the light-sensitive proteins to an excited state and causes the zinc finger protein – the molecule that targets DNA – to move to the target gene and transcribe to activate gene expression.

Once genes were expressed using the system, gene function and cell-to-cell interaction could be monitored. Gene regulation or tissue reconstruction could occur, which the authors suggest would be useful for research in biotechnology and medicine.

Quick to respond

“Some gene regulation systems respond in the timeframe of days, whereas LITEZ responds in hours. So, if you want to study a biological process that happens quickly, LITEZ would be a preferable choice,” said Gersbach.

“Similarly, the system would be useful for a gene therapy that needs to respond quickly to disease conditions.”

Molecular biologist Jacqueline Matthews at the University of Sydney, who was not involved in the study, said the ability to turn gene expression on and off using LITEZ is an advantage over current systems where gene expression stays on for extended periods once activated.

Could it be used in human treatments?

“The thing that’s particularly significant about this system as opposed to others is that it’s quite reversible, so you can switch on gene expression and then switch it off again,” she said.

However, Matthews said that, while this testing was done on a human cell culture, there might be difficulties in applying it to human treatment.

“You’ve got to be able to get a light source onto this system and the cells need to have been spiked with LITEZ that targets genes. If you were dealing with cells in a culture it would be easy, but in many cases I don’t know how you would get light on the right spots in actual people,” she said.

“If you were trying to make artificial skin or grow different organs you could potentially use this system at certain stages, but once you start treating solid tissues or existing organs in the body it would be quite tricky,” she said.

The benefits of using light

However, other experts point out that using light for gene regulation and expression eliminates the risk of toxicity or stray molecules that is apparent in chemical gene expression systems.

“This is really neat system that is general, in that it can specifically target any gene, and is mild, in that blue light is not harmful to cells,” said biological chemist Nicholas Dixon at the University of Wollongong, in Australia, who was not involved in the study.

“In contrast to some other, more conventional methods, it does not require addition of chemical compounds that might have confounding effects – all that is required is to turn the light on and off.”

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