AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands

作者：Gao R; Yan X; Zheng C; Goldsmith C M; Afione S; Hai B; Xu J; Zhou J; Zhang C; Chiorini J A; Baum B J; Wang S^*

来源：Gene Therapy, 2011, 18(1): 38-42.

DOI：10.1038/gt.2010.128

• salivary gland
• irradiation
• aquaporin-1
• AAV2

Previously (Shan et al, 2005), we reported that adenoviral vector-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to minipig parotid glands following irradiation (IR) transiently restored salivary flow to near normal levels. This study evaluated a serotype 2, adeno-associated viral (AAV2) vector for extended correction of IR (single dose; 20 Gy)-induced, parotid salivary hypofunction in minipigs. At 16 weeks following the IR parotid salivary flow decreased by 85-90%. AAV2hAQP1 administration at week 17 transduced only duct cells and resulted in a dose-dependent increase in salivary flow to similar to 35% of pre-IR levels (to similar to 1ml per 10 min) after 8 weeks (peak response). Administration of a control AAV2 vector or saline was without effect. Little change was observed in clinical chemistry and hematology values after AAV2hAQP1 delivery. Vector-treated animals generated high anti-AAV2 neutralizing antibody titers by week 4 (similar to 1:1600) and significant elevations in salivary (similar to 15%), but not serum, granulocyte macrophage colony-stimulating factor levels. Following vector administration, salivary [Na(+)] was dramatically increased, from similar to 10 to similar to 55 mM (at 4 weeks) and finally to 39 mM (8 weeks). The findings demonstrate that localized delivery of AAV2hAQP1 to IR-damaged parotid glands leads to increased fluid secretion from surviving duct cells, and may be useful in providing extended relief of salivary hypofunction in previously irradiated patients. Gene Therapy (2011) 18, 38-42; doi:10.1038/gt.2010.128; published online 30 September 2010

• 出版日期2011-1
• 单位首都医科大学