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利用唾液腺中的内分泌分泌途径进行全身基因治疗。

Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics.

作者信息

Voutetakis Antonis, Wang Jianghua, Baum Bruce J

机构信息

Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, DHHS, Bethesda, Maryland 20892-1190, USA.

出版信息

J Cell Physiol. 2004 Apr;199(1):1-7. doi: 10.1002/jcp.10429.

DOI:10.1002/jcp.10429
PMID:14978729
Abstract

Mammalian salivary glands are commonly used models of exocrine secretion. However, there is substantial experimental evidence showing the physiological existence of endocrine secretory pathways in these tissues. The use of gene transfer technology in vivo has allowed the unambiguous demonstration of these endocrine pathways. We and others have exploited such findings and evaluated salivary glands as possible target tissues for systemic applications of gene therapeutics. Salivary glands present numerous advantages for this purpose, including being well encapsulated, which limits extra-glandular vector dissemination, and having the luminal membranes of almost all parenchymal cells accessible via intraoral delivery of vectors through the main excretory ducts. Existing studies suggest that clinical benefits will result from salivary gland targeted systemic gene therapeutics.

摘要

哺乳动物的唾液腺是外分泌分泌的常用模型。然而,有大量实验证据表明这些组织中存在内分泌分泌途径。体内基因转移技术的应用使得这些内分泌途径得到了明确的证实。我们和其他人利用了这些发现,并评估了唾液腺作为基因治疗全身应用的可能靶组织。唾液腺为此目的具有许多优点,包括被良好包裹,这限制了腺体外载体的扩散,并且几乎所有实质细胞的腔膜可通过载体经主要排泄导管经口递送而接触到。现有研究表明,唾液腺靶向全身基因治疗将带来临床益处。

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1
Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics.利用唾液腺中的内分泌分泌途径进行全身基因治疗。
J Cell Physiol. 2004 Apr;199(1):1-7. doi: 10.1002/jcp.10429.
2
Salivary glands: novel target sites for gene therapeutics.唾液腺:基因治疗的新靶点
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Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders.唾液腺作为某些单基因内分泌疾病基因治疗的潜在基因转移靶点。
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Quantitative histochemical investigation of rat salivary gland at different age stages of involution of the endocrine system.内分泌系统不同退化年龄阶段大鼠唾液腺的定量组织化学研究。
Morphol Embryol (Bucur). 1983 Oct-Dec;29(4):229-35.
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Salivary glands as a model for craniofacial applications of gene transfer.唾液腺作为基因转移在颅面应用中的模型。
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[Endocrine aspects of the physiology of the salivary glands. I. Evidence of a possible salivary endocrine role].[唾液腺生理学的内分泌方面。I. 唾液可能具有内分泌作用的证据]
Rev Med Chil. 1972 Sep;100(9):1120-5.
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Protective MCMV immunity by vaccination of the salivary gland via Wharton's duct: replication-deficient recombinant adenovirus expressing individual MCMV genes elicits protection similar to that of MCMV.通过沃顿氏管(Wharton's duct)途径对唾液腺进行疫苗接种来实现保护性的巨细胞病毒(MCMV)免疫:表达单个 MCMV 基因的复制缺陷型重组腺病毒引发的保护作用与 MCMV 相似。
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Human parathyroid hormone is secreted primarily into the bloodstream after rat parotid gland gene transfer.
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Hum Gene Ther. 2011 Jan;22(1):84-92. doi: 10.1089/hum.2010.097. Epub 2011 Jan 3.
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Sorting of transgenic secretory proteins in rhesus macaque parotid glands after adenovirus-mediated gene transfer.腺病毒介导的基因转移后恒河猴腮腺中转基因分泌蛋白的分选
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Isoproterenol increases sorting of parotid gland cargo proteins to the basolateral pathway.异丙肾上腺素增加腮腺货物蛋白向基底外侧途径的分选。
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