Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression.
Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression.
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肽核酸靶向神经降压素受体并腹膜内施用。
DOI：
10.1073/pnas.96.12.7053
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发表时间：
1999
影响因子：
11.1
通讯作者：
E. Richelson
中科院分区：
文献类型：
--
作者：
B. M. Tyler;K. Jansen;D. Mccormick;Christopher L. Douglas;M. Boules;J. Stewart;Lihong Zhao;Benjamin W Lacy;B. Cusack;A. Fauq;E. Richelson
用凝胶漂移试验证明，大鼠神经降压素(NT)受体(NTR1)的mRNA未修饰的反义多肽核酸(PNA)确实存在于脑内，从而表明PNA确实越过了血脑屏障。一个IP地址。注射反义PNA可特异性抑制脑内微量注射NT的降温和抗伤害性反应。这些结果与NT在脑和小肠中的结合部位减少有关。此外，针对DNA的正义-NTR1PNA直接显微注射到大脑中，特异性地降低了50%的mRNA水平，并导致对NT的反应丧失。为了证明行为、结合和信使核糖核酸变化的特异性，用NTR1PNA处理的动物被测试了对吗啡的行为反应，并测定了它们的Mu受体水平。在这些NTR1PNA处理的动物中，两者都被发现没有受到影响。反义和正义PNA的作用都是完全可逆的。这项工作提供了证据，证明任何针对脑蛋白的反义策略都可以通过ip传递通过跨越正常的血脑屏障来发挥作用。同样重要的是，体内试验表明，一种名为正义PNA的抗基因策略可能是一种有效的治疗方法。
Intraperitoneal injection of an unmodified antisense peptide nucleic acid (PNA) complementary to mRNA of the rat neurotensin (NT) receptor (NTR1) was demonstrated by a gel shift assay to be present in brain, thus indicating that the PNA had in fact crossed the blood-brain barrier. An i.p. injection of this antisense PNA specifically inhibited the hypothermic and antinociceptive activities of NT microinjected into brain. These results were associated with a reduction in binding sites for NT both in brain and the small intestine. Additionally, the sense-NTR1 PNA, targeted to DNA, microinjected directly into the brain specifically reduced mRNA levels by 50% and caused a loss of response to NT. To demonstrate the specificity of changes in behavioral, binding, and mRNA studies, animals treated with NTR1 PNA were tested for behavioral responses to morphine and their mu receptor levels were determined. Both were found to be unaffected in these NTR1 PNA-treated animals. The effects of both the antisense and sense PNAs were completely reversible. This work provides evidence that any antisense strategy targeted to brain proteins can work through i. p. delivery by crossing the normal blood-brain barrier. Equally important was that an antigene strategy, the sense PNA, was shown in vivo to be a potentially effective therapeutic treatment.
DOI：
--
发表时间：
1997-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
G. Mardirossian;K. Lei;M. Rusckowski;F. Chang;T. Qu;M. Egholm;D. Hnatowich
通讯作者：
G. Mardirossian;K. Lei;M. Rusckowski;F. Chang;T. Qu;M. Egholm;D. Hnatowich
DOI：
10.1073/pnas.92.12.5592
发表时间：
1995-06
影响因子：
11.1
作者：
W. Pardridge;R. Boado;Young-Sook Kang
通讯作者：
W. Pardridge;R. Boado;Young-Sook Kang
人神经降压素受体基因多态性的鉴定。
影响因子：
8.9
作者：
Watson,M;Isackson,PJ;Makker,M;Yamada,MS;Yamada,M;Cusack,B;Richelson,E
通讯作者：
Richelson,E