A collaborative research team led by Chief Scientist Rikiya Watanabe and Research Scientist Hajime Shinoda from the RIKEN Pioneering Research Institute has successfully developed a testing technology capable of rapidly and directly detecting messenger RNA drugs (mRNA drugs) in blood as a measure against gene doping in racehorses and athletes. By further advancing their originally developed genetic testing method—which is the world's fastest and simplest—they have developed a new technology called the "Direct-SATORI method," which can detect mRNA drugs from one drop of blood within 10 minutes. Beyond doping countermeasures, this technology is expected to be applied to in vivo pharmacokinetic analysis and efficacy evaluation of mRNA therapeutics for underlying diseases such as infectious diseases and cancer. The results were published in the online edition of Analytical Chemistry on December 22.
There are growing concerns about "gene doping," in which genes are introduced into the body to enhance the competitive performance of racehorses and athletes. Gene doping testing was first implemented at the 2021 Tokyo Olympics.
The genetic materials conventionally used for doping mainly consist of DNA, and current testing also targets DNA.
On the other hand, with the technological advancement of mRNA drugs accompanying the COVID-19 pandemic, there are strong concerns about new gene doping that misuses this technology. mRNA drugs can temporarily express proteins in the body through the use of lipid nanoparticles (LNP) and modified RNA, but detection is extremely difficult because they are not integrated into the genome and are rapidly degraded.
Therefore, the research team improved the world's fastest and simplest genetic testing method, the "SATORI method," which Watanabe and his colleagues have recently developed. They created a new "Direct-SATORI method" capable of directly detecting mRNA drugs.
The "SATORI method" is the world's fastest genetic testing method and can quantitatively detect target RNA at the single-molecule level by combining CRISPR-Cas13 (enzyme) with a microchip containing integrated microscopic test tubes. It was developed by Watanabe and his colleagues in 2022.
In this study, the research group integrated a process for efficiently extracting genes from mRNA drugs into this method and developed the "new Direct-SATORI method," which also suppresses the effects of various components contained in blood.
With the new technology, mRNA drugs can be detected from one drop of blood within 10 minutes.
In validation experiments using horses, mRNA remaining in just 50µL of blood (equivalent to one drop) could be reliably detected up to approximately 24 hours after administration. This method is expected to be utilized in the medical field for real-time evaluation of therapeutic effects, optimization of dosage, and reduction of side effect risks.
Watanabe commented, "I am very pleased that the technology we developed for infectious disease testing through interdisciplinary collaborative research has evolved into gene doping testing. Going forward, I will continue to work hand in hand with Dr. Hajime Shinoda, a member of our laboratory, and collaborate with co-researchers and private companies to promote efforts toward social implementation."
Journal Information
Publication: Analytical Chemistry
Title: Direct Single-Molecule Detection of mRNA-LNP Drugs in Blood
DOI: 10.1021/acs.analchem.5c05862
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