Baxendale Sarah, van Eeden Freek, Wilkinson Robert
The Bateson Centre, Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK.
Department of Infection, Immunity and Cardiovascular Disease, Medical School, Beech Hill Rd, University of Sheffield, Sheffield, S10 2RX, UK.
Adv Exp Med Biol. 2017;1007:179-197. doi: 10.1007/978-3-319-60733-7_10.
The goal of personalised medicine is to develop tailor-made therapies for patients in whom currently available therapeutics fail. This approach requires correlating individual patient genotype data to specific disease phenotype data and using these stratified data sets to identify bespoke therapeutics. Applications for personalised medicine include common complex diseases which may have multiple targets, as well as rare monogenic disorders, for which the target may be unknown. In both cases, whole genome sequence analysis (WGS) is discovering large numbers of disease associated mutations in new candidate genes and potential modifier genes. Currently, the main limiting factor is the determination of which mutated genes are important for disease progression and therefore represent potential targets for drug discovery. Zebrafish have gained popularity as a model organism for understanding developmental processes, disease mechanisms and more recently for drug discovery and toxicity testing. In this chapter, we will examine the diverse roles that zebrafish can make in the expanding field of personalised medicine, from generating humanised disease models to xenograft screening of different cancer cell lines, through to finding new drugs via in vivo phenotypic screens. We will discuss the tools available for zebrafish research and recent advances in techniques, highlighting the advantages and potential of using zebrafish for high throughput disease modeling and precision drug discovery.
个性化医疗的目标是为那些现有治疗方法无效的患者开发量身定制的疗法。这种方法需要将个体患者的基因型数据与特定疾病的表型数据相关联，并使用这些分层数据集来确定定制疗法。个性化医疗的应用包括可能有多个靶点的常见复杂疾病，以及靶点可能未知的罕见单基因疾病。在这两种情况下，全基因组序列分析（WGS）正在新的候选基因和潜在修饰基因中发现大量与疾病相关的突变。目前，主要限制因素是确定哪些突变基因对疾病进展至关重要，因此是药物发现的潜在靶点。斑马鱼作为一种模式生物，在理解发育过程、疾病机制以及最近在药物发现和毒性测试方面越来越受欢迎。在本章中，我们将探讨斑马鱼在不断扩展的个性化医疗领域中可以发挥的各种作用，从生成人源化疾病模型到对不同癌细胞系进行异种移植筛选，再到通过体内表型筛选寻找新药。我们将讨论可用于斑马鱼研究的工具和技术的最新进展，强调使用斑马鱼进行高通量疾病建模和精准药物发现的优势和潜力。
