摘要
在过去的三十年中,基因治疗作为许多疾病的治疗的替代方法已经取得了相当大的进展。自2009年以来,已有一些对人体各种疾病的成功治疗的研究被报道。在临床前,动物模型模拟人类病情是非常重要的。例如,在基因治疗中,动物模型用于评估转基因表达的安全性、有效性、剂量、局部化等关于病毒载体的变量。然而,选择一个合适的特定疾病模型对于成功的临床转化是最重要的。本文重点在基因治疗研究中最常用的动物模型,如小鼠、犬、非人类灵长类动物、兔,猪和最近开发的人源化的小鼠。小动物和大动物作为特定疾病模型都有各自的优点和缺点,而其选择很大程度上基于研究类型和时间。小动物的寿命较短,可以非常适合于退化/老化的研究,寿命较长的大动物可以适应纵向研究,也有助于剂量调整,以最大限度地提高治疗效果。现在,人源化小鼠或人鼠嵌合体得到人体组织或细胞研究的关注,从而提供对治疗干预更可靠的认识。因此,为了评估在基因治疗临床试验前的安全性和有效性,动物模型对于新载体技术的体内测试是非常重要的。
关键词: 动物模型,基因治疗,基因疾病,病毒载体,人源化小鼠,临床试验。
Current Gene Therapy
Title:Contemporary Animal Models For Human Gene Therapy Applications
Volume: 15 Issue: 6
Author(s): Chitra Gopinath, Trupti Job Nathar, Arkasubhra Ghosh, Dennis Durand Hickstein and Everette Jacob Remington Nelson
Affiliation:
关键词: 动物模型,基因治疗,基因疾病,病毒载体,人源化小鼠,临床试验。
摘要: Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.
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Chitra Gopinath, Trupti Job Nathar, Arkasubhra Ghosh, Dennis Durand Hickstein and Everette Jacob Remington Nelson , Contemporary Animal Models For Human Gene Therapy Applications, Current Gene Therapy 2015; 15 (6) . https://dx.doi.org/10.2174/1566523215666150929110424
DOI https://dx.doi.org/10.2174/1566523215666150929110424 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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