Analytical technique for gene and cell doping could ensure ethics and fairness in sports
Sadie Harley
scientific editor
Robert Egan
associate editor
A research team has developed a high-throughput multiplexed gene and cell doping analysis (HiMDA) based on gene scissors (CRISPR-Cas). The work is in the journal Science Advances.
Unethical doping practices to enhance athletic performance are becoming more sophisticated with the use of advanced technology, and gene and cell doping—the use of gene or cell therapies to manipulate body functions—poses a serious threat to fairness in sports.
Gene-based drugs such as insulin-like growth factor (IGF-I) and erythropoietin (EPO), which can maximize strength and endurance, are likely to be abused by athletes in some sports as a means of performance enhancement.
The World Anti-Doping Agency (WADA) has prohibited this practice since 2003, but diagnostic techniques that can accurately identify gene and cell doping are still at an early stage.
Quantitative polymerase chain reaction (qPCR)-based gene testing has been piloted at the Tokyo Summer Olympics since the World Anti-Doping Agency first published guidelines for genetic doping in 2021.
Current protein-level doping analytical methods cannot clearly distinguish between exogenous genetic targets that produce proteins structurally identical to endogenous proteins. This has led to the need for new analytical platforms that can distinguish exogenous genes at the DNA level.
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Very trace amounts of doping genes and transgenic cell models spiked in blood are amplified directly without nucleic acid extraction, and the presence or absence of targets is then confirmed by sequence-dependent fluorescence reaction of Cas12a, a type of gene scissors. The entire analysis time from blood to readout is as short as 90 minutes. Credit: Korea Institute of Science and Technology (KIST) -
The advantage is that doping genes in blood can be amplified without nucleic acid extraction, reducing the time and labor required for extraction. This allows multiple blood samples to be processed simultaneously for high-throughput processing and analysis. Credit: Korea Institute of Science and Technology (KIST) -
The advantage is that doping genes in blood can be amplified without nucleic acid extraction, reducing the time and labor required for extraction. This allows multiple blood samples to be processed simultaneously for high-throughput processing and analysis. Credit: Korea Institute of Science and Technology (KIST)
The HiMDA directly amplifies the target gene from the blood without complex sample preparation, and then applies CRISPR-Cas, the Nobel Prize-winning gene editing technology, to determine the presence of the exogenous gene rapidly and precisely.
By injecting representative gene doping substances such as hGH, EPO, IGF-I into an experimental mouse model and applying the assay platform, the researchers were able to accurately detect exogenous genes at the 2.5 copies within 90 minutes using as little as 5 μL (microliters) of blood sample, less than half the size of a fingertip drop. This demonstrated superior performance in both sensitivity and specificity compared to existing assays.
The developed assay is not limited to doping tests, but is considered to be a platform-based diagnostic technology that can be applied to early diagnosis of infectious diseases, detection of antibiotic resistance genes, genetic disease testing, evaluation of cell therapy, drug adaptability, and precision medicine.
Currently, the technology is undergoing the certification process to be adopted as a World Anti-Doping Agency-approved method, and is attracting attention as a next-generation anti-doping testing platform that can respond to various new doping methods based on genes and proteins.
"By applying gene-editing technology to doping tests, this study provides a practical solution that can overcome the limitations of existing techniques and contribute to protecting sports ethics and fairness," said Changmin Sung, a principal researcher at the Doping Control Center at the Korea Institute of Science and Technology (KIST).
"It has the potential to develop into a core foundation for precision medicine and genetic diagnostic technologies in the future."
More information: Joon-Yeop Yi et al, High-throughput multiplexed gene and cell doping analysis through CRISPR-Cas12a system integrated with blood direct PCR, Science Advances (2025).
Journal information: Science Advances
