Heating up gene activation

There's a new technique for targeting gene therapy to specific tissues: sound waves that turn on gene expression, according to an article published online in PNAS. The technique could eventually also help orchestrate stem cell differentiation, the authors note. Currently scientists can control the timing of gene activation with techniques like ionizing radiation. They have also used small molecular switches to turn on gene expression. But ionizing radiation increases the risk of cancer, limitin

Tia Ghose

| 2 min read

There's a new technique for targeting gene therapy to specific tissues: sound waves that turn on gene expression, according to an article published online in PNAS. The technique could eventually also help orchestrate stem cell differentiation, the authors note. Currently scientists can control the timing of gene activation with techniques like ionizing radiation. They have also used small molecular switches to turn on gene expression. But ionizing radiation increases the risk of cancer, limiting the potential for repeated treatment, and molecular methods can't precisely control the location of gene expression. Chrit Moonen, a chemical physicist at the Center for National Scientific Research at the University Victor Segalen in Bordeaux, France, and his colleagues turned on gene expression by activating a heat sensitive promoter using high intensity ultrasound. To test the concept, they created transgenic mice that contained a bioluminescent gene controlled by a DNA region called the heat shock promoter 70 (HSP70). When a person gets a fever, this stretch of DNA boosts production of proteins that shield cells from damage. The team then focused high intensity ultrasound--sound waves above the audible range--on a region approximately 1/2 a millimeter in diameter in the leg muscles of the mice. Because the waves are focused on such a small area, researchers can target high levels of energy at precise locations in the body, said Moonen. The intense pulse heated up a tiny patch of tissue in the body to between 42 and 44 degrees Celsius. At the same time, they monitored the temperature using MRI thermometry to ensure the tissue didn't overheat. The group measured changes in the amount of light given off from the patch of muscle to detect gene expression. The use of MRI thermometry, was "a really nice addition," said Christopher Contag, a molecular biologist at Stanford University who was not involved in the study. Pei Zhong, a biomedical engineer at Duke University, also not a co-author, agreed. "They have a real-time measurement of the thermal dose while they are treating tissue," which was not available in prior studies, he said. The current study only activated genes in skeletal muscle cells close to the skin's surface. But future work should push the limits of the ultrasound technique to see whether it can work for deeper organs like the liver or the heart, Contag says. The technique may enable experts to one day precisely target therapy by activating genes only where needed, when needed, said Moonen. For instance, scientists could send pluripotent stem cells into a damaged heart and use the technique to activate expression of the genes that trigger the stem cells to differentiate into new heart cells. But Contag said that specific targeting may not be the best approach for most types of gene therapy. "Many times when we use gene therapy we don't know where we want the gene and we'd like the gene to correct deficiencies widely, not just treating tumors we can see but ones we can't see," he said.
**__Related stories:__*** linkurl:Stem Cells and Gene Therapy;http://www.the-scientist.com/article/display/53518/
[01 September 2007]* linkurl:Whither Gene Therapy;http://www.the-scientist.com/article/display/23064/
[01 February 2006]*linkurl:The Meaning of Epigenetics;http://www.the-scientist.com/article/display/18516/
[26 April 1999]

Heating up gene activation

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