期刊
HUMAN GENE THERAPY
卷 17, 期 11, 页码 1122-1133出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2006.17.1122
关键词
-
资金
- Intramural NIH HHS Funding Source: Medline
- NIEHS NIH HHS [N01-ES-75408] Funding Source: Medline
Before conducting a phase 1/2 clinical trial of a serotype 5 adenovirus encoding human aquaporin-1 (AdhAQP1) for the treatment of radiation-damaged salivary glands, we have conducted a detailed toxicity and biodistribution study in adult rats. AdhAQP1 (2 x 10(8)-2 x 10(11) particles) was delivered to a single submandibular gland by retroductal cannulation. Administration of this vector resulted in no animal mortality or morbidities, and no adverse signs of clinical toxicity. In addition, over the 92-day time course of the study, with both male and female rats, there were no consistent treatment-related changes in serum indicators of hepatic, renal, and cardiac functions. Importantly, we also observed no vector-associated effects on either water consumption by, or hematocrit levels in, study animals. However, three suggestive mild gender-related response differences were seen. Female, but not male, rats exhibited small reductions in food consumption (similar to 10-15%) and body weight gain (5-10%), and evidence of persistent inflammation, after vector treatment. These were vector, but not dose, related. Three days after delivery of 2 x 10(11) particles of AdhAQP1, vector was detected primarily in the targeted gland; 9 of 10 samples from the targeted gland were positive, whereas only 5 of 90 nonoral samples were positive. There was no evidence of the generation of replication-competent adenovirus in saliva or blood samples. In aggregate, these findings show that localized delivery of AdhAQP1 to salivary glands appears to occur without significant toxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据