With the increase in knowledge resulting from the sequencing of the human genome, the genetic basis for the underlying differences in individuals, their diseases, and how they respond to therapies is starting to be understood. This has formed the foundation for the era of precision medicine in many human diseases that is beginning to be implemented in the clinic, particularly in cancer. However, preclinical testing of therapeutic approaches based on individual biology will need to be validated in animal models prior to translation into patients. Although animal models, particularly murine models, have provided significant information on the basic biology underlying immune responses in various diseases and the response to therapy, murine and human immune systems differ markedly. These fundamental differences may be the underlying reason why many of the positive therapeutic responses observed in mice have not translated directly into the clinic. There is a critical need for preclinical animal models in which human immune responses can be investigated. For this, many investigators are using humanized mice, i.e., immunodeficient mice engrafted with functional human cells, tissues, and immune systems. We will briefly review the history of humanized mice, the remaining limitations, approaches to overcome them and how humanized mouse models are being used as a preclinical bridge in precision medicine for evaluation of human therapies prior to their implementation in the clinic.

中文翻译：

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免疫疾病和精密医学的人性化小鼠模型。

随着人类基因组测序知识的增加，人们开始理解潜在的个体差异，疾病基础以及他们对疗法的反应的遗传基础。这已经为许多人类疾病中的精密医学时代奠定了基础，这种疾病已开始在临床中开始应用，尤其是在癌症中。然而，在转化为患者之前，需要在动物模型中验证基于个体生物学的治疗方法的临床前测试。尽管动物模型（尤其是鼠模型）已经提供了有关各种疾病中免疫应答基础的基本生物学信息以及对治疗的应答​​的重要信息，但鼠和人的免疫系统却存在显着差异。这些根本的差异可能是为什么在小鼠中观察到的许多积极治疗反应尚未直接转化为临床的根本原因。迫切需要可以研究人类免疫应答的临床前动物模型。为此，许多研究人员正在使用人源化小鼠，即移植了功能性人类细胞，组织和免疫系统的免疫缺陷小鼠。我们将简要回顾人源化小鼠的历史，尚存的局限性，克服它们的方法，以及人源化小鼠模型如何在精密医学中用作临床前桥梁，以评估其在临床上的应用，从而对人类疗法进行评估。迫切需要可以研究人类免疫反应的临床前动物模型。为此，许多研究人员正在使用人源化小鼠，即移植有功​​能性人类细胞，组织和免疫系统的免疫缺陷小鼠。我们将简要回顾人源化小鼠的历史，尚存的局限性，克服它们的方法，以及人源化小鼠模型如何在精密医学中用作临床前桥梁，以评估其在临床上的应用，从而对人类疗法进行评估。迫切需要可以研究人类免疫反应的临床前动物模型。为此，许多研究人员正在使用人源化小鼠，即移植了功能性人类细胞，组织和免疫系统的免疫缺陷小鼠。我们将简要回顾人源化小鼠的历史，尚存的局限性，克服它们的方法，以及人源化小鼠模型如何在精密医学中用作临床前桥梁，以评估其在临床上的应用，从而对人类疗法进行评估。