【佳学基因检测】用于1型神经纤维瘤病基因解码的自发和基因工程动物模型

人体基因检测需要多少钱—比较

不断深化研究《肿瘤靶向药物选择的基因突变标准》时，神经科疾病基因解码团队《Int J Mol Sci》在 2021 Feb 16;22(4):1954发表了一篇题目为《1型神经纤维瘤病的自发和工程大型动物模型》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Sara H Osum, Adrienne L Watson, David A Largaespada 等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

基因工程,大型动物, 1型神经纤维瘤病,自发的,靶向治疗。

肿瘤靶向治疗基因检测临床应用结果

动物模型对于了解人类疾病生物学包括疾病发生的基因原因和开发新疗法至关重要。迄今为止，用于研究人类疾病普遍问题最常见的动物是小鼠。小鼠模型是强大的研究工具，因为它们体积小、寿命有限和明确的基因信息背景使研究人员能够轻松地操纵它们的基因组并在一般实验室空间中维持大量动物。然而，正是这些属性使它们与人类如此不同，并部分解释了为什么这些模型不能准确预测人类患者的药物反应。神经纤维瘤病 (NFs) 尤其如此，这是一组使个体易患神经系统肿瘤的遗传疾病，其中最常见的是 1 型神经纤维瘤病 (NF1)。尽管进行了多年的研究，但对于1 型神经纤维瘤病 (NF1)，仍有许多未解决的问题和有效的治疗方法。基因工程小鼠极大地提高了我们对1 型神经纤维瘤病 (NF1)的许多方面的理解，但它们并不能说明疾病的整体复杂性，并且由于体型和生理学的差异，一些研究成果不能很好地应用于临床治疗。此外，1 型神经纤维瘤病 (NF1)小鼠模型严重依赖 Cre-Lox 系统，该系统不能准确反映伴随人类肿瘤发展的杂合性自发丧失的分子机制。自发和基因工程大型动物模型可能为啮齿动物1 型神经纤维瘤病 (NF1) 研究提供有价值的补充。自然发生的疾病比较模型具有有吸引力的前景，因为它们发生在不同的遗传背景上，并且是由于自发突变而不是工程突变。使用患有自然疾病的动物对研究骨肉瘤、淋巴瘤和糖尿病是有效的。自发性神经纤维瘤病样症状包括神经纤维瘤和恶性外周神经鞘瘤 (MPNST) 已在几种大型动物物种中记录，并与人类1 型神经纤维瘤病 (NF1)具有生物学和临床相似性。这些动物可以提供对1 型神经纤维瘤病 (NF1)复杂生物学的更多见解，并可能为临床前试验提供平台。此外，最近开发了1 型神经纤维瘤病 (NF1)的基因工程猪模型，并显示出与 NF1 患者相似的各种临床特征。它们的大尺寸和相对较长的使用寿命允许纵向成像研究和使用人体设备评估创新手术技术。与人类更大的遗传、解剖学和生理学相似性使得能够对在人类患者中发现的精确疾病等位基因进行工程改造，并使其成为在患者临床试验之前对小分子、细胞和基因疗法进行临床前药代动力学和药效学研究的理想选择。人类和患有自然疾病的动物之间的比较基因组研究，以及大型动物疾病模型的临床前研究，可能有助于确定治疗干预的新靶点并加快新疗法的转化。在《1 型神经纤维瘤病 (NF1)的基因检测基础：动物模型基因解码》中，神经纤维瘤病的基因解码基因检测团队讨论了新的 NF1 基因工程大型动物模型和大型动物自发性 NF 样表现的病例，特别强调了这些比较模型如何充当专门的小鼠模型和 NF1 患者之间的关键转化中介。

肿瘤发生与复发转移国际数据库描述：

Animal models are crucial to understanding human disease biology and developing new therapies. By far the most common animal used to investigate prevailing questions about human disease is the mouse. Mouse models are powerful tools for research as their small size, limited lifespan, and defined genetic background allow researchers to easily manipulate their genome and maintain large numbers of animals in general laboratory spaces. However, it is precisely these attributes that make them so different from humans and explains, in part, why these models do not accurately predict drug responses in human patients. This is particularly true of the neurofibromatoses (NFs), a group of genetic diseases that predispose individuals to tumors of the nervous system, the most common of which is Neurofibromatosis type 1 (NF1). Despite years of research, there are still many unanswered questions and few effective treatments for NF1. Genetically engineered mice have drastically improved our understanding of many aspects of NF1, but they do not exemplify the overall complexity of the disease and some findings do not translate well to humans due to differences in body size and physiology. Moreover, NF1 mouse models are heavily reliant on the Cre-Lox system, which does not accurately reflect the molecular mechanism of spontaneous loss of heterozygosity that accompanies human tumor development. Spontaneous and genetically engineered large animal models may provide a valuable supplement to rodent studies for NF1. Naturally occurring comparative models of disease are an attractive prospect because they occur on heterogeneous genetic backgrounds and are due to spontaneous rather than engineered mutations. The use of animals with naturally occurring disease has been effective for studying osteosarcoma, lymphoma, and diabetes. Spontaneous NF-like symptoms including neurofibromas and malignant peripheral nerve sheath tumors (MPNST) have been documented in several large animal species and share biological and clinical similarities with human NF1. These animals could provide additional insight into the complex biology of NF1 and potentially provide a platform for pre-clinical trials. Additionally, genetically engineered porcine models of NF1 have recently been developed and display a variety of clinical features similar to those seen in NF1 patients. Their large size and relatively long lifespan allow for longitudinal imaging studies and evaluation of innovative surgical techniques using human equipment. Greater genetic, anatomic, and physiologic similarities to humans enable the engineering of precise disease alleles found in human patients and make them ideal for preclinical pharmacokinetic and pharmacodynamic studies of small molecule, cellular, and gene therapies prior to clinical trials in patients. Comparative genomic studies between humans and animals with naturally occurring disease, as well as preclinical studies in large animal disease models, may help identify new targets for therapeutic intervention and expedite the translation of new therapies. In this review, we discuss new genetically engineered large animal models of NF1 and cases of spontaneous NF-like manifestations in large animals, with a special emphasis on how these comparative models could act as a crucial translational intermediary between specialized murine models and NF1 patients.