New research results could improve gene therapy
(PhysOrg.com) -- Many diseases are the result of defective genes, and gene therapy is the tantalizing prospect of inserting properly functioning genes into a sick patient. But many promising gene therapies falter after a few weeks, and lasting cures remain elusive.
Why these new genes get turned off in patients is not completely understood. A new paper published in Nature by a Brigham Young University professor and colleagues at Stanford may give fundamental insights into how to prevent these genes from being turned off and could lead to new therapies that last much longer.
The highly regulated dance of genes being turned on and turned off at the appropriate time is what leads to the development of the human body, said Steven M. Johnson, BYU assistant professor of molecular biology and second author on the paper. At certain times, some genes are tightly packaged and cant be turned on, while at other times they are more loosely packed and accessible. Our work shares more details about how this packaging works.
Johnson began work on the project while a post-doctoral researcher at the Stanford School of Medicine in the lab of Nobel laureate Andrew Fire. The data-intensive study required the same level of persistence that Johnson showed when, after being rejected for three consecutive years by the University of Utah School of Medicine, he eventually earned a Ph.D. in 2004 from Yale University.
The intricate bundling of DNA is required to fit six feet of DNA in the tiny six micron-wide nucleus of every cell in the body. For perspective, if a nucleus were the size of a hockey puck, the comparable DNA would be 16 miles long.
Thats why, at any given time, many genes are buried inside the tightly wound package of DNA and arent accessible by the triggers that could connect to them to turn them on.
A key part of the bundling process is tiny units inside the nucleus, which are like spools wrapped with DNA thread.
The Stanford/BYU study created a map of the positions of these units throughout the entire human genome, which includes 3 billion base pairs of DNA. This level of understanding is essential to creating methods to keep the target genes involved in gene therapy from getting turned off after a few weeks.
From what were learning in this study, we might be able to fix the silencing of these genes involved in gene therapy if thats due to them being bundled, Johnson said. Researchers could try to re-position the packaging to keep things in an open DNA state instead of a closed DNA state.
Provided by Brigham Young University
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