O'Connell A C, Baccaglini L, Fox P C, O'Connell B C, Kenshalo D, Oweisy H, Hoque A T, Sun D, Herscher L L, Braddon V R, Delporte C, Baum B J
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer Gene Ther. 1999 Nov-Dec;6(6):505-13. doi: 10.1038/sj.cgt.7700078.
This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 x 10(9) or 1 x 10(8) plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.
本研究评估了单次向成年恒河猴腮腺注射编码人水通道蛋白-1的重组腺病毒（AdhAQP1）的安全性和有效性。鉴于该病毒可能用于临床治疗唾液腺的辐射损伤，将AdhAQP1（剂量为2×10⁹或1×10⁸蚀斑形成单位/腺体）经导管注射到受照射腺体及其对侧未受照射的腺体中。辐射（单次剂量，10 Gy）显著降低了暴露腺体的唾液分泌量。病毒注射导致基因转移到受照射和未受照射的腺体中，且所有动物均未出现不良的局部（唾液）或全身（血清化学、全血细胞计数）效应。然而，AdhAQP1注射的效果存在差异，在这些实验条件下，并非对所有动物的唾液流速都产生一致的积极影响。我们得出结论，单次腺病毒介导的基因转移至灵长类动物唾液腺耐受性良好，尽管其在增强受照射腮腺液体分泌方面的功能效用并不稳定。
