Several rAAV Vectors Efficiently Cross the Blood-brain Barrier and Transduce Neurons and Astrocytes in the Neonatal Mouse Central Nervous System
Several rAAV Vectors Efficiently Cross the Blood-brain Barrier and Transduce Neurons and Astrocytes in the Neonatal Mouse Central Nervous System
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DOI：
10.1038/mt.2011.98
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发表时间：
2011-08-01
影响因子：
12.4
通讯作者：
Gao, Guangping
中科院分区：
文献类型：
--
作者：
Zhang, Hongwei;Yang, Bin;Gao, Guangping
向中枢神经系统（CNS）的无创全身基因传递在很大程度上受到血脑屏障（BBB）的阻碍。最近的研究记录了重组腺相关病毒 9 (rAAV9) 血管内递送后广泛的中枢神经系统基因转移。为了研究用于跨 BBB 系统性基因传递的替代且可能更有效的 rAAV 载体，我们系统地评估了九种不同的 rAAVEGFP 载体在新生小鼠血管内输注后的 CNS 基因转移特性。多种 rAAV 可有效转导神经元、运动神经元、星形胶质细胞和浦肯野细胞；其中，rAAVrh.10 在许多检查区域中至少与 rAAV9 一样有效。重要的是，静脉注射 rAAV 不会引起中枢神经系统异常小胶质细胞增生。在中枢神经系统中实现稳定广泛基因转移的 rAAV 是开发影响中枢神经系统大部分区域的神经系统疾病的治疗方法的非常有用的平台，也是神经科学研究的便利生物工具。
Noninvasive systemic gene delivery to the central nervous system (CNS) has largely been impeded by the blood-brain barrier (BBB). Recent studies documented widespread CNS gene transfer after intravascular delivery of recombinant adeno-associated virus 9 (rAAV9). To investigate alternative and possibly more potent rAAV vectors for systemic gene delivery across the BBB, we systematically evaluated the CNS gene transfer properties of nine different rAAVEGFP vectors after intravascular infusion in neonatal mice. Several rAAVs efficiently transduce neurons, motor neurons, astrocytes, and Purkinje cells; among them, rAAVrh.10 is at least as efficient as rAAV9 in many of the regions examined. Importantly, intravenously delivered rAAVs did not cause abnormal microgliosis in the CNS. The rAAVs that achieve stable widespread gene transfer in the CNS are exceptionally useful platforms for the development of therapeutic approaches for neurological disorders affecting large regions of the CNS as well as convenient biological tools for neuroscience research.