Spencer Brian J, Verma Inder M
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7594-9. doi: 10.1073/pnas.0702170104. Epub 2007 Apr 26.
Treatment of many neuronal degenerative disorders will require delivery of a therapeutic protein to neurons or glial cells across the whole CNS. The presence of the blood-brain barrier hampers the delivery of these proteins from the blood, thus necessitating a new method for delivery. Receptors on the blood-brain barrier bind ligands to facilitate their transport to the CNS; therefore, we hypothesized that by targeting these receptors, we may be able to deliver proteins to the CNS for therapy. Here, we report the use of the lentivirus vector system to deliver the lysosomal enzyme glucocerebrosidase and a secreted form of GFP to the neurons and astrocytes in the CNS. We fused the low-density lipoprotein receptor-binding domain of the apolipoprotein B to the targeted protein. This approach proved to be feasible for delivery of the protein and could possibly be used as a general method for delivery of therapeutic proteins to the CNS.
许多神经元退行性疾病的治疗需要将治疗性蛋白质递送至整个中枢神经系统（CNS）的神经元或神经胶质细胞。血脑屏障的存在阻碍了这些蛋白质从血液中的递送，因此需要一种新的递送方法。血脑屏障上的受体结合配体以促进其向中枢神经系统的转运；因此，我们推测通过靶向这些受体，或许能够将蛋白质递送至中枢神经系统进行治疗。在此，我们报告了使用慢病毒载体系统将溶酶体酶葡萄糖脑苷脂酶和一种分泌形式的绿色荧光蛋白（GFP）递送至中枢神经系统的神经元和星形胶质细胞。我们将载脂蛋白B的低密度脂蛋白受体结合结构域与靶向蛋白融合。这种方法被证明对于蛋白质的递送是可行的，并且可能用作将治疗性蛋白质递送至中枢神经系统的通用方法。
