Middaugh C R, Evans R K, Montgomery D L, Casimiro D R
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047, USA.
J Pharm Sci. 1998 Feb;87(2):130-46. doi: 10.1021/js970367a.
The advent of gene therapy and polynucleotide-based vaccines has resulted in the use of plasmid DNA as a drug substance. Although biologically (cell or animal) based assays must currently be employed to establish the identity and potency of such drugs, we argue that in the future, a combination of microchip-based mutation detection devices combined with an array of chromatographic, electrophoretic, hydrodynamic, and spectroscopic methods can be employed to rigorously establish these properties. We review a variety of such methods in this context and also consider the issue of the chemical stability of plasmids. Extensive comparison is made to protein-based pharmaceuticals with the unique importance of polynucleotide sequence emphasized in comparison to protein tertiary structure.
基因治疗和基于多核苷酸的疫苗的出现，使得质粒DNA被用作药物。尽管目前必须采用基于生物学（细胞或动物）的检测方法来确定此类药物的身份和效力，但我们认为，未来可以将基于微芯片的突变检测设备与一系列色谱、电泳、流体动力学和光谱方法结合使用，以严格确定这些特性。我们在此背景下综述了各种此类方法，并考虑了质粒的化学稳定性问题。与基于蛋白质的药物进行了广泛比较，强调了多核苷酸序列相对于蛋白质三级结构的独特重要性。
