Fighting Cancer Through DNA Programming
New technology developed by a research team at the University of Delaware could lead to the development of new cancer therapies, as well as other drugs. The technology enables DNA strands to be programmed into switches that turn proteins on and off. The results of this DNA programming have been published on March 12 in Nature Chemistry and described by the Wilfred Chen Group.
Whereas digital media are made up of ones and zeroes, DNA has four key components: the nucleotides guanine, adenine, cytosine, and thymine. The output is the protein, and the arrangement of these four parts determines it. In this study, the DNA code has been repurposed to design logic-gated DNA circuits.
Proteins were created and purified in the lab while strands of DNA with a custom sequence were ordered from a manufacturer. The protein was then attached to the DNA, resulting in protein-DNA conjugates.
DNA circuits were then tested on E. coli bacteria and human cells. In accordance with the group’s design, the target proteins organized, assembled and disassembled.
“Previous work has shown how powerful DNA nanotechnology might possibly be, and we know how powerful proteins are within cells,” Rebecca said. “We managed to link those two together.”
Drug delivery applications
Until cancer prodrugs are metabolized into their therapeutic form, they remain inactive. The DNA circuits had been designed by the team to control the activity of a protein that was responsible for converting the prodrug into its active form. The DNA circuit and protein activity remained at an off state unless switched on by specific RNA/DNA sequence inputs.
The sequence inputs made by the scientists were based on microRNA, which are small RNA molecules responsible for regulating cellular gene expression. MicroRNA in cancer cells are known to have irregularities absent in healthy cells.
The team calculated the manner in which nucleotides are arranged to trigger the cancer prodrug in the presence of cancer microRNA. Where microRNA is missing, the cancer prodrug should stay non-toxic and inactive in a non-cancerous environment. Cells were incapable of growing when the cancer microRNAs were present and able to switch the DNA circuit on. Conversely, with the circuit off, cells were able to grow normally.
“This is based on a very simple concept, a logical combination, but we are the first to make it work,” said Wilfred Chen.
The technology could go beyond cancer. Down the road, researchers have the potential to simply plug and play programmed DNA into a variety of cells to combat a number of illnesses.
DNA programming can even be applied to the production of biofuels, accomplished by breaking down a plant fiber using a series of chemical reactions.
“It can address a wide scope of problems, and that makes it very intriguing,” said Wilfred.