Researchers from the Institute of Integrated Cell-Material Sciences (iCeMS) at Kyoto University have designed a set of DNA-based molecules capable of controlling biological networks in cells. Their study, published in Nature's Scientific Reports, may one day help to reprogram cells and treat human diseases, such as cancer and HIV. The team, led by Namasivayam Ganesh Pandian, a research associate at the institute, seeks to create tools to restore order in cells whose biological programs have gone haywire.
"The human genome contains approximately 20,000 genes, which act as recipes for making proteins," said Ganesh. "At any given time, different combinations of these genes are being turned on and off to enable cells to perform their jobs in a process known as epigenetic regulation. This system is remarkably precise. However, if oversight is lost, the checks and balances in cells fail resulting in disease."
By fusing an epigenetic drug known as SAHA, which switches genes to an "on state", with a programmable DNA-based molecule, PIP, capable of targeting specific regions of the genome, the scientists created a set of about 32 small molecules called SAHA-PIPs.
"The PIPs serve as homing devices for SAHA to be more effective," added Junichi Taniguchi, another author involved in the study. "Best of all, they are tunable, meaning that we can tinker with them to change their targets."
After adding the panel of SAHA-PIPs to human skin cells, the researchers found that each molecule could activate distinct and therapeutically important sets of genes involved in different physiological processes. The SAHA-PIPs were also safe and did not cause any toxicity in the cells at the concentrations tested.
"The hope is that we can one day harness the unique ability of these SAHA-PIPs to cure currently untreatable diseases where the switches for gene regulation have failed," said Hiroshi Sugiyama, the principal investigator of the study.
Extenal LinkDistinct DNA-based Epigenetic Switches Trigger Transcriptional Activation of Silent Genes in Human Dermal Fibroblasts
Ganesh N. Pandian1*, Junichi Taniguchi2*, Syed Junetha2, Shinsuke Sato1, Le Han2, Abhijit Saha2, Chandran AnandhaKumar2, Toshikazu Bando2, Hiroki Nagase3,4, Thangavel Vaijayanthi2, Rhys D. Taylor2 & Hiroshi Sugiyama1,2
Scientific Reports | Published Online 24 January 2014 | DOI: 10.1038/srep03843
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo, Kyoto 606-8502, Japan
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8501, Japan
Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo 173-8610, Japan
Division of Cancer Genetics, Chiba Cancer Center, Research Institute, 666-2 Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8717, Japan.