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通过直接插管小鼠下颌下唾液腺后,不同病毒载体介导的基因转移。

Gene transfer mediated by different viral vectors following direct cannulation of mouse submandibular salivary glands.

作者信息

Shai Ela, Falk Haya, Honigman Alik, Panet Amos, Palmon Aaron

机构信息

Department of Oral Biology, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.

出版信息

Eur J Oral Sci. 2002 Jun;110(3):254-60. doi: 10.1034/j.1600-0722.2002.21200.x.

Abstract

The salivary gland has been suggested as an accessible organ for gene transfer to express recombinant proteins locally in the saliva, as well as for secretion to the blood circulation. The aim of this study was to evaluate the efficiency of gene transfer to salivary glands using different viral vectors: adenovirus, vaccinia, herpes simplex type 1 (HSV), and two retroviral vectors (murine leukemia virus (MuLV) and lentivirus). We show, by in situ staining and beta-galactosidase reporter activity assay, that the adenoviral and vaccinia vectors were able to deliver the reporter gene efficiently to acinar and duct cells. The HSV vector was less efficient and infected only the acinar cells. The lentiviral vector infected acinar and duct cells, but at a relatively low efficiency. The MuLV vector did not infect the salivary gland unless cell proliferation was induced. Host immune responses to viral infection, inflammation, apoptosis and lymphocyte infiltration, in the transduced glands, were assessed. The DNA viral vectors induced local lymphocyte infiltration and apoptosis. In contrast, the retroviral vectors did not induce an immune response. Our results describe the outcome of salivary gland infection with each of the five different viral vectors and indicate their advantages and limitations for transferring genes to the salivary glands.

摘要

唾液腺已被认为是一种便于进行基因转移的器官,可在唾液中局部表达重组蛋白,也可分泌至血液循环中。本研究的目的是评估使用不同病毒载体(腺病毒、痘苗病毒、1型单纯疱疹病毒(HSV)以及两种逆转录病毒载体(鼠白血病病毒(MuLV)和慢病毒))向唾液腺进行基因转移的效率。通过原位染色和β-半乳糖苷酶报告基因活性测定,我们发现腺病毒载体和痘苗病毒载体能够有效地将报告基因传递至腺泡细胞和导管细胞。HSV载体效率较低,仅感染腺泡细胞。慢病毒载体可感染腺泡细胞和导管细胞,但效率相对较低。除非诱导细胞增殖,MuLV载体不会感染唾液腺。我们评估了转导腺体中宿主对病毒感染、炎症、凋亡和淋巴细胞浸润的免疫反应。DNA病毒载体可诱导局部淋巴细胞浸润和凋亡。相比之下,逆转录病毒载体不会诱导免疫反应。我们的结果描述了用五种不同病毒载体分别感染唾液腺的结果,并指出了它们在向唾液腺转移基因方面的优势和局限性。

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