Soudais C, Laplace-Builhe C, Kissa K, Kremer E J
Généthon III/CNRS 1923, Evry, France.
FASEB J. 2001 Oct;15(12):2283-5. doi: 10.1096/fj.01-0321fje. Epub 2001 Aug 17.
In the central nervous system (CNS), there are innate obstacles to the modification of neurons: their relative low abundance versus glia and oligodendrocytes, the inaccessibility of certain target populations, and the volume one can inject safely. Our aim in this study was to characterize the in vivo efficacy of a novel viral vector derived from a canine adenovirus (CAV-2). Here we show that CAV-2 preferentially transduced i) rat olfactory sensory neurons; ii) rodent CNS neurons in vitro and in vivo; and, more clinically relevant, iii) neurons in organotypic slices of human cortical brain. CAV-2 also showed a high disposition for retrograde axonal transport in vivo. We examined the molecular basis of neuronal targeting by CAV-2 and suggest that due to CAR (coxsackie adenovirus receptor) expression on neuronal cells-and not oligodendrocytes, glia, myofibers, and nasal epithelial cells-CAV-2 vectors transduced neurons preferentially in these diverse tissues.
在中枢神经系统（CNS）中，神经元的修饰存在先天障碍：与神经胶质细胞和少突胶质细胞相比，它们的丰度相对较低，某些目标群体难以接近，以及能够安全注射的体积有限。我们在本研究中的目的是表征一种源自犬腺病毒（CAV-2）的新型病毒载体的体内功效。在此我们表明，CAV-2优先转导：i）大鼠嗅觉感觉神经元；ii）体外和体内的啮齿动物中枢神经系统神经元；以及，更具临床相关性的是，iii）人类大脑皮质器官型切片中的神经元。CAV-2在体内还显示出对逆行轴突运输的高度倾向。我们研究了CAV-2靶向神经元的分子基础，并表明由于神经元细胞（而非少突胶质细胞、神经胶质细胞、肌纤维和鼻上皮细胞）上表达柯萨奇腺病毒受体（CAR），CAV-2载体在这些不同组织中优先转导神经元。
