Neuberger Elmo W I, Simon Perikles
Med Sport Sci. 2017;62:91-106. doi: 10.1159/000465456. Epub 2017 Jun 2.
The advent of gene transfer technologies in clinical studies aroused concerns that these technologies will be misused for performance-enhancing purposes in sports. However, during the last 2 decades, the field of gene therapy has taken a long and winding road with just a few gene therapeutic drugs demonstrating clinical benefits in humans. The current state of gene therapy is that viral vector-mediated gene transfer shows the now long-awaited initial success for safe, and in some cases efficient, gene transfer in clinical trials. Additionally, the use of small interfering RNA promises an efficient therapy through gene silencing, even though a number of safety concerns remain. More recently, the development of the molecular biological CRISPR/Cas9 system opened new possibilities for efficient and highly targeted genome editing. This chapter aims to define and consequently demystify the term "gene doping" and discuss the current reality concerning gene- and cell-based physical enhancement strategies. The technological progress in the field of gene therapy will be illustrated, and the recent clinical progress as well as technological difficulties will be highlighted. Comparing the attractiveness of these technologies with conventional doping practices reveals that current gene therapy technologies remain unattractive for doping purposes and unlikely to outperform conventional doping. However, future technological advances may raise the attractiveness of gene doping, thus making it easier to develop detection strategies. Currently available detection strategies are introduced in this chapter showing that many forms of genetic manipulation can already be detected in principle.
基因转移技术在临床研究中的出现引发了人们的担忧,即这些技术可能会被滥用于体育领域的提高成绩目的。然而,在过去的20年里,基因治疗领域走过了漫长而曲折的道路,只有少数基因治疗药物在人体中显示出临床益处。目前基因治疗的现状是,病毒载体介导的基因转移在临床试验中展现出了期待已久的初步成功,实现了安全的基因转移,在某些情况下还具有高效性。此外,尽管仍存在一些安全问题,但小干扰RNA的使用有望通过基因沉默实现高效治疗。最近,分子生物学CRISPR/Cas9系统的发展为高效且高度靶向的基因组编辑开辟了新的可能性。本章旨在定义并进而揭开“基因兴奋剂”这一术语的神秘面纱,并讨论当前基于基因和细胞的身体增强策略的实际情况。将阐述基因治疗领域的技术进展,并突出近期的临床进展以及技术难题。将这些技术与传统兴奋剂使用方法的吸引力进行比较后发现,目前的基因治疗技术对于兴奋剂使用目的而言仍缺乏吸引力,并且不太可能比传统兴奋剂更具优势。然而,未来的技术进步可能会提高基因兴奋剂的吸引力,从而使开发检测策略变得更加容易。本章将介绍目前可用的检测策略,表明原则上许多形式的基因操作已经可以被检测到。