Ledley F D
GENEMEDICINE, INC., Woodlands, Texas 77381, USA.
Pharm Res. 1996 Nov;13(11):1595-614. doi: 10.1023/a:1016420102549.
The pharmaceutical approach to somatic gene therapy is based on consideration of a gene as a chemical entity with specific physical, chemical and colloidal properties. The genes that are required for gene therapy are large molecules (> 1 x 10(6) Daltons, > 100 nm diameter) with a net negative charge that prevents diffusion through biological barriers such as an intact endothelium, the plasma membrane or the nuclear membrane. New methods for gene therapy are based on increasing knowledge of the pathways by which DNA may be internalized into cells and traffic to the nucleus, pharmaceutical experience with particulate drug delivery systems, and the ability to control gene expression with recombined genetic elements. This article reviews two themes in the development of gene therapies: first, the current approaches involving the administration of cells, viruses and plasmid DNA; second, the emerging pharmaceutical approach to gene therapy based on the pharmaceutical characteristics of DNA itself and methods for advanced drug delivery.
体细胞基因治疗的药学方法基于将基因视为具有特定物理、化学和胶体性质的化学实体这一考量。基因治疗所需的基因是大分子（> 1×10⁶道尔顿，直径> 100纳米），带有净负电荷，这阻止了其通过诸如完整内皮、质膜或核膜等生物屏障进行扩散。基因治疗的新方法基于对DNA可内化进入细胞并转运至细胞核的途径的深入了解、颗粒药物递送系统的药学经验以及利用重组遗传元件控制基因表达的能力。本文综述了基因治疗发展中的两个主题：第一，当前涉及细胞、病毒和质粒DNA给药的方法；第二，基于DNA自身药学特性和先进药物递送方法的新兴基因治疗药学方法。
