Smith A E
Genzyme Corporation, Framingham, Massachusetts 01701, USA.
Annu Rev Microbiol. 1995;49:807-38. doi: 10.1146/annurev.mi.49.100195.004111.
The use of DNA as a drug is both appealing and simple in concept. Indeed in many instances the feasibility of such an approach has been established using model systems. In practical terms, however, the delivery of DNA to human tissues presents a wide variety of problems that differ with each potential therapeutic application. In this review, the design, production, and application of viral vectors for human gene therapy are considered. Although viral vectors are an obvious starting point because viruses have evolved efficient mechanisms to introduce and express their nucleic acid into recipient cells, by the same token the viral hosts have evolved sophisticated mechanisms to rid themselves of such pathogens. The challenge for the therapeutic use of viral vectors is to achieve efficient and often extended expression of the exogenous gene while evading the host defenses. Methodology used and progress towards that goal are reviewed.
将DNA用作药物在概念上既具有吸引力又很简单。实际上，在许多情况下，使用模型系统已经证实了这种方法的可行性。然而，从实际角度来看，将DNA递送至人体组织存在各种各样的问题，这些问题因每种潜在的治疗应用而异。在这篇综述中，我们考虑了用于人类基因治疗的病毒载体的设计、生产和应用。尽管病毒载体是一个显而易见的起点，因为病毒已经进化出了将其核酸导入并在受体细胞中表达的有效机制，但同样地，病毒宿主也进化出了复杂的机制来清除这些病原体。病毒载体治疗应用面临的挑战是在规避宿主防御的同时实现外源基因的高效且通常是持续的表达。本文综述了为此目的所使用的方法及其进展。
