de Lima Maria C Pedroso, da Cruz M Teresa Girao, Cardoso Ana L C, Simoes Sérgio, de Almeida Luís Pereira
Department of Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Apartado 3126, 3001-401 Coimbra, Portugal.
Curr Drug Targets CNS Neurol Disord. 2005 Aug;4(4):453-65. doi: 10.2174/1568007054546144.
Due to the presence of the blood-brain barrier, the central nervous system (CNS) is not easily accessible to systemically delivered macromolecules with therapeutic activity such as growth factors, cytokines or enzymes. Therefore, the expression of exogenously administered genes in the brain has been proposed for a wide variety of inherited and acquired diseases of the CNS, for which classical pharmacotherapy is unavailable or not easily applicable. Gene therapy to the CNS has been the target of a great number of studies aiming at finding a viable therapeutic strategy for the treatment of neurological disorders. This approach has already been used as a promising tool for brain protection and repair from neuronal insults and degeneration in several animal models, and is currently being applied in clinical trials. The choice of an appropriate vector system for transferring the desired gene into the affected brain area is an important issue for developing a safe and efficient gene therapy approach for the CNS. In this review, we focus on the various types of vectors that have been used for gene delivery into the CNS. Particular emphasis is given to their mode of preparation, biological activity, safety and in vivo behavior. Examples illustrating the potential of both viral and non-viral vectors in therapeutic applications to brain disorders are provided. In addition, the use of lentiviral vectors for in vivo modeling of genetic disorders of the CNS is discussed.
由于血脑屏障的存在，全身递送具有治疗活性的大分子（如生长因子、细胞因子或酶）难以进入中枢神经系统（CNS）。因此，对于中枢神经系统的多种遗传性和获得性疾病（传统药物治疗无效或不易应用），已提出在脑内表达外源基因的方法。中枢神经系统基因治疗一直是大量研究的目标，旨在寻找治疗神经疾病的可行治疗策略。在几种动物模型中，这种方法已被用作保护大脑和修复神经元损伤及退变的有前景的工具，目前正在临床试验中应用。选择合适的载体系统将所需基因转移到受影响的脑区，是开发安全有效的中枢神经系统基因治疗方法的一个重要问题。在本综述中，我们重点关注已用于向中枢神经系统递送基因的各种载体类型。特别强调了它们的制备方式、生物学活性、安全性和体内行为。提供了说明病毒载体和非病毒载体在脑疾病治疗应用中的潜力的实例。此外，还讨论了慢病毒载体在中枢神经系统遗传性疾病体内建模中的应用。
