Vidalin Olivier, Muslmani Machadiya, Estienne Clément, Echchakir Hamid, Abina Amine M
NOKAD, F-91058 Evry, France.
Curr Opin Pharmacol. 2009 Oct;9(5):669-76. doi: 10.1016/j.coph.2009.06.017. Epub 2009 Jul 29.
Most diseases have multifactorial origins and their study requires complex in vivo validation strategies selected for their particular relevance. Most of the in vivo models used to date have been selected according to their availability and the accessibility of the corresponding technology platform. With the rapid development of new technologies, an increasing number of relevant systems for in vivo target validation are now available. In this review, we present in vivo loss-of-function tools acting at three biological levels (the gene, the messenger RNA and the protein); we discuss the specificity of each strategy and how the three techniques can be combined during the validation process in order to overcome the limitations of each one. Thus, combination will broaden the spectrum of the available validation systems and will enable target validation that predicts the situation in humans as accurately as possible.
大多数疾病都有多种因素起源，对它们的研究需要根据其特定相关性选择复杂的体内验证策略。迄今为止使用的大多数体内模型都是根据其可用性和相应技术平台的可及性来选择的。随着新技术的快速发展，现在有越来越多相关的体内靶点验证系统可供使用。在本综述中，我们介绍了作用于三个生物学水平（基因、信使核糖核酸和蛋白质）的体内功能丧失工具；我们讨论了每种策略的特异性，以及在验证过程中如何将这三种技术结合起来以克服每种技术的局限性。因此，结合将拓宽可用验证系统的范围，并能够尽可能准确地预测人类情况的靶点验证。
