A new method for early disease detection using DNA droplets

-.Credit: Tokyo Institute of Technology

The formation of water droplets by liquid-liquid phase separation (or core selvation) in macromolecules is a hot topic in life science research. Among these various macromolecules that form droplets, DNA is very interesting because it is predictable and programmable. This is a useful quality in nanotechnology. Recently, the programmable nature of DNA was used to construct and control DNA droplets formed by core selvation of sequence-designed DNA.

A group of scientists at Tokyo University of Technology (Tokyo Institute of Technology), led by Professor Masahiro Takigami, have developed computational DNA droplets capable of recognizing specific combinations of chemically synthesized microRNAs (miRNAs) that act as biomarkers for tumors. Did. Using these miRNAs as molecular inputs splash Physical DNA droplet phase separation can provide DNA logic computing output. Professor Takinoue explains the need for such research as follows. Biological system It regulates their function by combining biosensing and molecular logic operations. There is no literature on the integration of DNA droplets and molecular calculations. ” Advanced functional materials..

The development of this DNA droplet required a series of experiments. First, they designed three Y-shaped DNA nanostructures called Y motifs A, B, and C, with three sticky ends, and created DNA droplets of A, B, and C. .. Normally, similar droplets bind automatically, but different droplets require a special “linker” molecule. So we used a linker molecule to bond the A droplet to the B and C droplets. These linker molecules were called AB linkers and AC linkers, respectively.

In their first experiment, they evaluated the “AND” operation of the AB droplet mixture by introducing two input DNAs. With this operation, the presence of an input is recorded as 1 and the absence of an input is recorded as 0. Phase separation of the AB droplet mixture occurred only at (1,1). That is, the presence of both input DNAs indicates a successful AND application. Surgery. Following this study, scientists decided to introduce the breast cancer tumor markers miRNA-1 and miRNA-2 into the AC droplet mixture as an input for the AND operation. The AND operation was successful. This means that the calculated DNA droplets have identified miRNAs.

In subsequent experiments, the team demonstrated simultaneous AND and NOT operations on AB mixtures with miRNA-3 and miRNA-4 breast cancer biomarkers. Finally, they created an ABC droplet mixture and introduced all four breast cancer biomarkers into this solution. The phase separation of ABC droplets depends on the cleavage of the linker, resulting in two-phase separation or three-phase separation.

This property of ABC droplets allowed researchers to demonstrate their ability to detect a set of known cancer biomarkers and simultaneously detect markers for three diseases. The corresponding author, Professor Takinoue, sees the great potential of computational DNA droplets. According to him, “If we can develop a DNA droplet that can process multiple inputs and outputs in an integrated manner, we can use it for early disease detection and drug delivery systems. Current research is in intelligent development research. It also functions as a foothold. Artificial cells and molecular robots. ”

Scientists have constructed “DNA droplets” containing designed DNA nanostructures

For more information:
Jing Gong et al, Computational DNA Droplet Recognizing MiRNA Sequence Input Based on Liquid-Liquid Phase Separation, Advanced functional materials (2022). DOI: 10.1002 / adfm.202202322

Quote: Https: // A new method for early disease detection using DNA droplets obtained on June 3, 2022 ( June 3, 2022)

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A new method for early disease detection using DNA droplets

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