Resende R R, Torres H A M, Yuahasi K K, P Majumder, H Ulrich
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil.
Drug Target Insights. 2007;2:183-96. Epub 2007 Aug 9.
The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference and aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affinity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs.
过去几十年中声名狼藉的生物技术进步使得理解基因分子机制的实验方法和新的治疗方法得以发展。基因治疗正在成熟为一种可行的实用方法，有治愈多种人类疾病的潜力。现在有一些基于核酸的药物可通过抑制基因表达或其基因产物的活性来控制遗传疾病的进展。新的治疗策略采用了广泛的分子工具，如含有转基因插入片段的细菌质粒、RNA干扰和适体。基于核酸的组成赋予了较低的免疫原性潜力，并且由于对大分子种类的高严格筛选，这些药物对其靶点具有高亲和力和选择性。然而，核酸的生物稳定性较差，因此需要进行化学修饰和递送系统来维持其活性并促进其细胞内化。本综述讨论了基于核酸的疗法（如适体和RNA干扰）的一些作用机制和应用，以及治疗性寡核苷酸的细胞摄取和细胞内递送平台及其权衡。
