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首页> 外文期刊>Molecular therapy: the journal of the American Society of Gene Therapy >Prolonged transgene expression in murine salivary glands following non-primate lentiviral vector transduction.
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Prolonged transgene expression in murine salivary glands following non-primate lentiviral vector transduction.

机译：非灵长类慢病毒载体转导后，小鼠唾液腺中转基因表达延长。

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摘要

Salivary glands are an accessible organ for gene therapy, enabling expression of recombinant proteins for both exocrine and endocrine secretion. Lentivirus-based vectors have many advantages for gene therapy, including their ability to infect nondividing cells and to stably integrate into the host genome, enabling long-term transgene expression without eliciting an inflammatory immune response. In the present study, murine salivary glands were inoculated with feline immunodeficiency virus (FIV)-based lentiviral vectors expressing various reporter genes. Luciferase expression was observed as early as 24 h posttransduction, peaked at 17-21 days, and remained stable for more than 80 days. Staining with X-gal suggested that mucous acinar cells were effectively transduced. FIV vector transduction with the secreted alkaline phosphatase gene increased serum levels in treated animals for up to 45 days, and the FIV vector harboring the interferon-gamma (IFN-gamma) expression cassette induced an increase in IFN-gamma serum levels as well as in the supernatant of salivary gland explant cultures. These results demonstrate that the transduction of salivary glands with nonprimate lentiviral vectors may provide a novel and highly effective vehicle for long-term endocrine transgene expression.
机译：唾液腺是用于基因治疗的可及器官，能够表达用于外分泌和内分泌的重组蛋白。基于慢病毒的载体在基因治疗中具有许多优势，包括它们感染非分裂细胞并稳定整合到宿主基因组中的能力，从而能够长期表达转基因而不会引起炎症性免疫反应。在本研究中，用表达各种报道基因的基于猫免疫缺陷病毒（FIV）的慢病毒载体接种鼠唾液腺。荧光素酶表达早在转导后24小时就观察到，在17-21天达到峰值，并保持稳定超过80天。用X-gal染色表明粘液腺泡细胞被有效地转导。用分泌的碱性磷酸酶基因进行的FIV载体转导可延长治疗动物的血清水平长达45天，带有干扰素-γ（IFN-γ）表达盒的FIV载体可诱导IFN-γ血清水平的升高以及在小鼠体内的升高。唾液腺外植体培养物的上清液。这些结果表明，用非灵长类慢病毒载体转导唾液腺可为长期内分泌转基因表达提供新颖且高效的载体。

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