AsianScientist (Mar. 20, 2019) – In a study published in Scientific Reports, researchers at Osaka University, Japan, have invented a device that can be used to detect drugs that get incorporated into DNA. Their findings have implications for assessing the efficacy of anticancer treatments.
Approximately one in three individuals will develop cancer at some point in life, underscoring a need for novel and effective treatments. While researchers are constantly developing new and improved therapies to kill cancer cells, or at least halt their replication, the precise molecular mechanisms by which a drug elicits anticancer effects may be obscure.
For example, trifluridine is an anticancer drug that gets incorporated into DNA as a cancer cell replicates. However, exactly where trifluridine inserts itself into the DNA remains a mystery because it is not distinguished by traditional DNA sequencing methods, hampering efforts to fully understand and develop the technology.
In this study, researchers led by Professor Masateru Taniguchi of Osaka University in Japan found a way to distinguish trifluridine from normal nucleotides in short strands of DNA. Using microscopic probes, the researchers passed an electrical current across a distance approximately 65,000 times smaller than a grain of sand—a gap just wide enough to fit a strand of DNA.
“Using this single-molecule quantum sequencing method, we successfully identified individual molecules in the DNA based on differences in electrical conductance,” explained lead author Dr. Takahito Ohshiro of Osaka University. “For the first time, we were able to directly detect anticancer drug molecules incorporated in the DNA.”
Importantly, the conductance of trifluridine was lower than that of the four native nucleotides, allowing it to easily be distinguished in the DNA sequence. Based on these values, the researchers successfully sequenced single DNA strands of up to 21 nucleotides, pinpointing the exact insertion sites of trifluridine.
“Now that we have the ability to determine exactly where the drug is incorporated, we can develop a better understanding of the mechanism involved in DNA damage,” said Taniguchi. “We expect that this technology will aid in the rapid development of new and more effective anticancer drugs.”
The article can be found at: Ohshiro et al. (2019) Direct Analysis of Incorporation of an Anticancer Drug into DNA at Single-Molecule Resolution.
Source: Osaka University.
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