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Animal Models for Target Diseases in Gene Therapy — using DNA and siRNA Delivery Strategies

机译：基因治疗中目标疾病的动物模型-使用DNA和siRNA传递策略

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摘要

Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmacokinetics within the setting of the wide variety of in vivo animal models now used. This critical appraisal of the recent literature sets out the different models that are currently being investigated to bridge from studies in cell lines through towards clinical reality. Whilst many scientists will be familiar with rodent (murine, fecine, cricetine, and musteline) models, few probably think of fish as a clinically relevant animal model, but zebrafish, madake, and rainbow trout are all being used. Larger animal models include rabbit, cat, dog, and cow. Pig is used both for the prevention of foot-and-mouth disease and human diseases, sheep is a model for corneal transplantation, and the horse naturally develops arthritis. Non-human primate models (macaque, common marmoset, owl monkey) are used for preclinical gene vector safety and efficacy trials to bridge the gap prior to clinical studies. We aim for the safe development of clinically effective delivery systems for DNA and RNAi technologies.
机译：纳米粒子，包括导致脂质复合物，脂质体和聚合物复合物的脂质多胺，是当前寻找多核酸成功递送系统的靶向药物载体系统。这篇综述的重点是基因和siRNA传递对目前使用的多种体内动物模型中功效，药效学和药代动力学研究的影响。对最新文献的严格评估提出了目前正在研究的不同模型，以将细胞系研究贯穿于临床现实。尽管许多科学家会熟悉啮齿动物（鼠，胎，牛尾草和鼬）模型，但很少有人认为鱼是临床上相关的动物模型，但是斑马鱼，疯子和虹鳟鱼都被使用了。较大的动物模型包括兔子，猫，狗和牛。猪用于预防口蹄疫和人类疾病，绵羊是角膜移植的典范，马自然发展为关节炎。在临床研究之前，将非人类灵长类动物模型（猕猴，普通are猴，猫头鹰猴）用于临床前基因载体安全性和有效性试验，以弥合差距。我们致力于安全开发适用于DNA和RNAi技术的临床有效递送系统。

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