DIRECT IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO SALIVARY-GLANDS
DIRECT IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO SALIVARY-GLANDS
复制标题
DOI：
10.1152/ajpgi.1994.266.6.g1146
复制
发表时间：
1994-06-01
影响因子：
--
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
--
作者：
MASTRANGELI, A;OCONNELL, B;CRYSTAL, RG
基因转移到唾液腺具有治疗唾液腺疾病和将治疗性蛋白质递送到口腔和上胃肠道的潜力。将重组腺病毒载体Ad.RSV beta gal [编码细胞内蛋白β-半乳糖苷酶（β-Gal）]和Ad alpha 1AT [编码人α（1）-抗胰蛋白酶（α（1）-AT），一种分泌蛋白]给予唾液腺细胞系，在体外证实了外源基因表达。在体内将Ad.RSV β gal载体逆行导管注射到大鼠唾液腺中导致β-Gal在腺泡和导管细胞中表达。腺病毒α 1AT在体内暴露于下颌下腺导致α 1-AT mRNA转录本的表达，α 1-AT的从头合成，并分泌到唾液中。为了评估腺病毒介导的基因转移到人腺体的可行性，用腺病毒RSV β gal离体感染人小唾液腺，并植入严重联合免疫缺陷小鼠。对人体组织的评价证实了β-Gal活性。这些观察结果表明，腺病毒载体能够直接传递基因到唾液腺，这表明了各种可能的基因治疗应用。
Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSV beta gal [coding for the intracellular protein beta-galactosidase (beta-Gal)] and Ad alpha 1AT [coding for human alpha(1)-antitrypsin (alpha(1)-AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSV beta gal vector to rat salivary glands in vivo resulted in beta-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Ad alpha 1AT resulted in expression of alpha(1)-AT mRNA transcripts, de novo synthesis of alpha(1)-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSV beta gal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated beta-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications.