Sport and Specialised Analytical Services, LGC, Newmarket Road, Fordham, Cambridgeshire, CB7 5WW, UK.
British Horseracing Authority, Holborn Gate, 26 Southampton Buildings, London, WC2A 1AN, UK.
Gene Ther. 2024 Sep;31(9-10):477-488. doi: 10.1038/s41434-024-00462-0. Epub 2024 Jul 7.
Gene doping, which includes the non-therapeutic use of genes or genetic elements that have the capacity to enhance athletic performance, is prohibited in horseracing and equestrian sports. To provide a comprehensive assessment of matrix and detection techniques, a custom adeno-associated virus serotype 8 vector was designed to include PCR binding sites for multiple target genes and assay types. The vector was injected via an intramuscular route into two Thoroughbred horses and matrices collected at defined timepoints. DNA was analysed using 3 detection methods: qPCR, digital PCR, and NGS. Overall, there was a strong correlation across the different detection methods employed, although digital PCR was less sensitive at lower concentrations. High concentrations of vector were detected at early timepoints in plasma and whole blood, which rapidly dropped after 0.5 d to trace levels by 4 d and 9 d post-administration respectively, following a similar pattern to previous studies. Vector was detected in dried blood spots at lower levels than whole blood, but with a similar detection time. Detection in hair root bulbs in one horse was observed at over a month post-administration, which opens new avenues for future gene doping testing in humans and animals.
基因兴奋剂,包括非治疗性使用基因或具有增强运动表现能力的遗传元件,在赛马和马术运动中是被禁止的。为了全面评估基质和检测技术,设计了一种定制的腺相关病毒血清型 8 载体,该载体包含多个靶基因和检测类型的 PCR 结合位点。载体通过肌肉内途径注射到两匹纯种马中,并在规定的时间点收集基质。使用 3 种检测方法分析 DNA:qPCR、数字 PCR 和 NGS。总的来说,尽管数字 PCR 在较低浓度时的灵敏度较低,但不同检测方法之间存在很强的相关性。在早期,载体在血浆和全血中的浓度较高,在给药后 0.5 天迅速下降到痕量水平,4 天和 9 天分别,与之前的研究相似。载体在干血斑中的检测水平低于全血,但检测时间相似。在一匹马的发根球中观察到给药一个多月后的检测结果,这为未来人类和动物的基因兴奋剂检测开辟了新的途径。