Non-viral Vectors for Gene Therapy
Non-viral Vectors for Gene Therapy
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DOI：
10.1007/978-3-030-41333-0_2
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Clévio Nóbrega;Liliana S. Mendonça;Carlos A. Matos
中科院分区：
文献类型：
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作者：
Clévio Nóbrega;Liliana S. Mendonça;Carlos A. Matos
目前，已有3400多个基因与疾病相关[1]，其中一些疾病是衰弱的、致命的，并且没有任何有效的治疗选择，随着基因组研究的进展，这个数字预计在未来十年内会增加。基因治疗是一种治疗策略，旨在针对疾病背后的基因，以治愈患者。因此，这种方法有望通过操作缺陷基因、移除或沉默病理基因或添加缺失的基因来建立治疗病因而不是症状的疗法。然而，这些雄心勃勃的策略受到了几个问题的阻碍，例如一些已开发的方法缺乏安全性和有效性，这可以用大多数基因操作工具的本质来解释。例如，裸露的DNA质粒在生物体液中迅速降解，它们无法有效地穿过细胞膜，因此无法到达目标细胞，它们激活免疫系统，免疫系统被编程来识别和消除含有外来遗传信息的载体[2]。因此，虽然大量的临床前和临床研究都是使用裸核酸进行的，但使用递送载体会产生更好的结果，即因为它们保护了核酸不受核酸酶降解的影响，并增加了细胞内的递送。尽管如此，尽管在过去几十年里在基因治疗策略方面做出了巨大努力，但很少有基于基因治疗的药物或治疗产品进入市场，这表明在基因治疗载体领域仍有很多工作要做。
Presently, more than 3400 genes have been associated with diseases [1], some of these pathologies are debilitating, mortal, and without any effective therapeutic options, and this number is expected to increase in the next decade as genomic studies advance. Gene therapy is a therapeutic strategy that seeks to target the genes behind the disorders in order to cure patients. Thus, this approach holds the promise of establishing therapies that treat the causes, rather than the symptoms, by manipulating deficient genes, removing or silencing pathologic genes, or adding missing genes. However, these ambitious strategies have been hampered by several problems, such as the lack of safety and efficiency of some of the developed approaches, which can be explained by the very nature of most gene-manipulating tools. Naked DNA plasmids, for example, are rapidly degraded in biological fluids, they are unable to efficiently cross the cellular membranes and therefore reach the target cells and they activate the immune system, which is programmed to identify and eliminate vehicles containing foreign genetic information [2]. Thus, although a large number of preclinical and clinical studies have been performed using naked nucleic acids, the use ofdelivery vectorsyields better results, namely because they protect the nucleic acids from nuclease degradation and increase intracellular delivery. Still, despite the big efforts made in the last decades with gene therapy strategies, very few gene therapy-based drugs or therapeutic products have reached the market, revealing that much still has to be done in the field of vectors for gene therapy.