Gene doping, defined as the misuse of gene transfer technologies to enhance athletic performance, poses a growing challenge to both sporting ethics and athlete safety. Traditional detection strategies, such as PCR-based assays, aim to identify the presence of foreign genetic material but are highly vulnerable to sequence alterations and localized gene expression. Despite regulatory bans by bodies like the World Anti-Doping Agency (WADA), no standardized detection method currently exists that can reliably identify gene doping in practice. This paper proposes the hypothesis that transcriptomic and microRNA (miRNA) profiling of peripheral blood mononuclear cells (PBMCs) can reveal a distinct molecular signature indicative of erythropoietin (EPO) gene doping. This “biological footprint” of gene doping, unlike direct transgene detection, reflects systemic changes in gene expression that persist longer and are more difficult to conceal. It is further hypothesized that these transcriptomic changes can be integrated into the Athlete Biological Passport framework, allowing for personalized longitudinal monitoring of athletes. This approach may overcome key limitations of current methods, offering both a broader detection window and resistance to evasion tactics. However, implementation must address the confounding effects of physiological variability due to training, altitude exposure, and individual genetics. Establishing robust statistical baselines and reference datasets will be critical to distinguishing genuine doping signatures from natural fluctuations. If validated, this strategy could transform anti-doping surveillance by focusing not on the genetic agent itself, but on its systemic biological impact, providing a powerful new tool for preserving fairness and safety in sport.
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