Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse.
Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse.
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DOI：
10.3389/fnana.2014.00042
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发表时间：
2014
影响因子：
2.9
通讯作者：
Vulchanova L
中科院分区：
文献类型：
--
作者：
Schuster DJ;Dykstra JA;Riedl MS;Kitto KF;Belur LR;McIvor RS;Elde RP;Fairbanks CA;Vulchanova L
腺相关病毒血清9型(AAV9)介导的基因转移在中枢神经系统(CNS)和周围组织中已有报道。本研究比较了鞘内注射后绿色荧光蛋白(GFP)在小鼠中枢神经系统和部分外周组织中的表达模式。或静脉注射(静注)等量单链AAV9载体的投递。在IT之后。在所有脊髓水平的脊髓神经元、初级传入纤维和相应的初级感觉神经元均可观察到GFP免疫反应阳性(-ir)。在背根神经节(DRG)的大小神经元以及三叉神经和迷走神经初级传入神经元中均可观察到较强的信号转导。静脉注射后感觉神经节的转导效率显著降低。治疗过的小鼠。在大脑中，静脉注射。注射后GFP免疫反应阳性(-ir)主要分布在三叉神经脊束、垂体以及散在的孤立神经元和星形胶质细胞中。相比之下，在IT之后。出生后，GFP-ir广泛分布于整个中枢神经系统，与3周相比，6周时GFP-ir的强度更高，神经纤维样染色更丰富。GFP-ir显著的脑区包括脑神经核团、腹侧脑桥、小脑皮质、海马体、垂体、脉络丛，以及选定的中脑、丘脑和下丘脑核团。在大脑皮层，GFP-ir与血管相关，在神经元和星形胶质细胞中均可见。在外周，结肠和回肠的GFP-ir存在于两种静脉注射的肠道神经系统。和IT。治疗过的小鼠。肝脏和肾上腺皮质，但没有肾上腺髓质，也显示丰富的GFP-ir后，两种途径。总而言之，IT。给药在感觉神经元和中枢神经系统产生更高的转导效率。使用这两种途径将可比性基因转移到外周组织的观察表明，I.T.输送的载体从蛛网膜下腔重新分布到体循环。
Adeno-associated virus serotype 9 (AAV9)-mediated gene transfer has been reported in central nervous system (CNS) and peripheral tissues. The current study compared the pattern of expression of Green Fluorescent Protein (GFP) across the mouse CNS and selected peripheral tissues after intrathecal (i.t.) or intravenous (i.v.) delivery of equivalent doses of single-stranded AAV9 vector. After i.t. delivery, GFP immunoreactivity (-ir) was observed in spinal neurons, primary afferent fibers and corresponding primary sensory neurons at all spinal levels. Robust transduction was seen in small and large dorsal root ganglion (DRG) neurons as well as trigeminal and vagal primary afferent neurons. Transduction efficiency in sensory ganglia was substantially lower in i.v. treated mice. In brain, i.v. delivery yielded GFP-immunoreactivity (-ir) primarily in spinal trigeminal tract, pituitary, and scattered isolated neurons and astrocytes. In contrast, after i.t. delivery, GFP-ir was widespread throughout CNS, with greater intensity and more abundant neuropil-like staining at 6 weeks compared to 3 weeks. Brain regions with prominent GFP-ir included cranial nerve nuclei, ventral pons, cerebellar cortex, hippocampus, pituitary, choroid plexus, and selected nuclei of midbrain, thalamus and hypothalamus. In cortex, GFP-ir was associated with blood vessels, and was seen in both neurons and astrocytes. In the periphery, GFP-ir in colon and ileum was present in the enteric nervous system in both i.v. and i.t. treated mice. Liver and adrenal cortex, but not adrenal medulla, also showed abundant GFP-ir after both routes of delivery. In summary, i.t. delivery yielded higher transduction efficiency in sensory neurons and the CNS. The observation of comparable gene transfer to peripheral tissues using the two routes indicates that a component of i.t. delivered vector is redistributed from the subarachnoid space to the systemic circulation.
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影响因子：
5.5
作者：
Kollarik, M.;Carr, M. J.;Undem, B. J.
通讯作者：
Undem, B. J.
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
5.3
作者：
Garg, Saurabh K.;Lioy, Daniel T.;Mandel, Gail
通讯作者：
Mandel, Gail
影响因子：
4.6
作者：
Dayton RD;Wang DB;Klein RL
通讯作者：
Klein RL
影响因子：
2.5
作者：
Gautron, Laurent;Sakata, Ichiro;Udit, Swalpa;Zigman, Jeffrey M.;Wood, John N.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.