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Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate

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机构: [1]Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, Guangdong Province, China [2]Department of Anesthesiology, Jiangxi Maternal and Child Health Hospital, Nanchang, 330000, Jiangxi Province, China [3]Department of Anesthesiology, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510120, Guangdong Province, China [4]Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, 07013, USA
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关键词: Neuropathic pain RNA interference Small interfering RNA Neuronal nitric oxide synthase (nNOS) Cell penetrating peptides

摘要:
We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to target nNOS. The feasibility, stability, efficiency and selectivity of this peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the new method with conventional siRNA carrier Lipofectamine (TM). It was found that the CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA, wow), which maintained stable in serum for as long as 4 h. The CPP Tat-LK15 was low-toxicity to cells, as the apoptosis rate of treat cells was not increased significantly when the used peptide lower than 10 mu g/mL. Moreover, the cellular uptake of nNOS siRNA by Rat Neurons-dorsal spinal cord (RNdsc) cells was also significantly more than naked siRNA by RNdsc cells. The CPP Tat-LK15 was an efficient and stable, and non-cytotoxic siRNA delivery to neurons and effectively silenced the nNOS expression. The CPP Tat-LK15 mediated siRNA delivery was a potential tool to treat neuropathic diseases involving NO or nNOS neurotoxic cascades. (C) 2017 Elsevier B.V. All rights reserved.

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出版当年[2016]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
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大类 | 4 区 医学
小类 | 4 区 神经科学
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Q3 NEUROSCIENCES
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Q3 NEUROSCIENCES

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第一作者机构: [1]Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, Guangdong Province, China
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通讯机构: [1]Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, Guangdong Province, China [*1]Department of Anesthesiology, Guangzhou GeneralHospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, 510010,Guangdong Province, China.
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