Gene transfer to muscle.
Gene transfer to muscle.
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基因转移到肌肉。
DOI：
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发表时间：
1996
影响因子：
3.9
通讯作者：
G. Dickson
中科院分区：
文献类型：
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作者：
G. Dickson
在人类中，骨骼肌肉组织可以构成超过50%的体重，并且一系列解剖学、生理学和细胞特征使得该组织成为用于基因转移程序的有吸引力的候选者，所述基因转移程序被设计为增强正常基因功能、表达异源治疗产物或免疫宿主生物体。在正常情况下，骨骼肌纤维是稳定的有丝分裂后细胞，具有良好的血管分布，必要时具有高再生能力。组织很容易获得，用于遗传载体的管理，必要时用于去除治疗区域。此外，肌纤维是源自称为卫星细胞的单核干细胞（或前体细胞）融合的多核细胞。肌纤维的合胞体性质意味着有限的基因递送到少数细胞核可能导致同源基因产物在相当大的区域上表达，并且在组织培养中卫星细胞的工程化允许通过移植和融合到现有肌纤维细胞中的离体基因转移的有效机制。已经提出将遗传物质转移到骨骼肌用于遗传性神经肌肉疾病，例如杜氏肌营养不良症（DMD），用于影响粘多糖、碳水化合物、氨基酸或脂质代谢的病症，用于常见的获得性病症，例如糖尿病、糖尿病和心血管疾病，以及用于针对许多感染因子的疫苗接种。广泛的基因转移技术现已应用于肌肉组织。一方面，存在基于病毒的载体系统。病毒已经进化出高效的机制来逃避宿主的免疫防御并将其遗传物质递送到细胞核，并且大量的研究已经针对利用这些特性来使用遗传修饰病毒递送外源基因。由于基因治疗的主要目的是长期表达，因此关键调控病毒基因的缺失对于确保复制缺陷和感染不会导致靶细胞死亡至关重要。
In humans the skeletal musculature can constitute over 50% of the body mass, and a range of anatomical, physiological and cellular features makes this tissue an attractive candidate for gene transfer procedures designed to augment normal gene function, express heterologous therapeutic products or immunize the host organism. Under normal conditions, skeletal myofibres are stable post-mitotic cells with good vascularity and, if necessary, high regenerative capacity. Tissues are easily accessible for administration of genetic vehicles and, if necessary, for removal of treated areas. In addition, myofibres are multinucleated cells deriving from the fusion of mononucleate stem (or precursor) cells known as satellite cells. The syncytial nature of the myofibres means that limited gene delivery to a few nuclei may lead to expression of the cognate gene product over a considerable area, and that engineering of satellite cells in tissue culture allows an efficient mechanism of ex vivo gene transfer via transplantation and fusion into existing myofibre cells. The transfer of genetic material to skeletal muscle has been proposed for inherited neuromuscular diseases such as Duchenne muscular dystrophy (DMD), for disorders affecting mucopolysaccharide, carbohydrate, amino acid or lipid metabolism, for common acquired disorders such as diabetes mellitus, hyperlipidaemia and cardiovascular disease, and for vaccination against a number of infectious agents. An extensive range of gene transfer techniques have now been applied to muscle tissues. On the one hand there are virus-based vector systems. Viruses have evolved highly efficient mechanisms for evading the host immune defence and delivering their genetic material to the nucleus, and an immense amount of research has been directed at harnessing these properties to deliver foreign genes using genetically modified viruses. As the major objective of gene therapy is long-term expression, deletion of key regulatory viral genes is essential to ensure replication deficiency and that infection does not lead to target cell death.