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| Recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream |
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| Author(s): Yamano S, Huang LY, Ding CT, Chiorini JA, Goldsmith CM, Wellner RB, Golding B, Kotin RM, Scott DE, Baum BJ |
| Source: HUMAN GENE THERAPY Volume: 13 Issue: 2 Pages: 287-298 Published: JAN 2002 |
| Times Cited: 22 References: 57 |
| Abstract: We have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (rAAVhIL10). IL-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. Human IL-10 (hIL-10) production was virus dose dependent after in vitro infection of HSG cells, a human submandibular gland cell line. The vector-derived hIL-10 produced was biologically active, as the medium from rAAVhIL10-infected HSG cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout mice challenged with heat-killed Brucella abortus. Administration of rAAVhIL10 (10(10) genomes per gland) to both mouse submandibular glands led to hIL-10 secretion into the bloodstream (similar to1-5 pg/ml), that is, in an endocrine manner, which was stable for similar to2 months. Salivary gland administration of rAAVhIL10 under experimental conditions was more efficacious than intravenous administration (similar to0.5-0.7 pg/ml). Also, hIL-10 was readily secreted in vitro from organ cultures of minced submandibular glands infected with rAAVhIL10, 6 or 8 weeks earlier. Consistent with these results, hIL-10 mRNA was detected by reverse transcription-polymerase chain reaction in submandibular glands of mice infected with rAAVhIL10 but not from control mice. At these doses, little to no hIL-10 was detected in mouse saliva. Using a rAAV serotype 2 vector encoding beta-galactosidase, we observed that the primary parenchymal target cells were ductal. These findings represent the first report of rAAV use to target exocrine glands for systemic secretion of a therapeutic protein, and support the notion that rAAV serotype 2 vectors may be useful in salivary glands for local (periglandular) and systemic gene-based protein therapeutics. |
| Document Type: Article |
| Language: English |
| Reprint Address: Baum, BJ (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1N113, Bethesda, MD 20892 USA |
Addresses:
1. NIDCR, GTTB, NIH, Bethesda, MD 20892 USA
2. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA
3. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA |
| Publisher: MARY ANN LIEBERT INC PUBL, 2 MADISON AVENUE, LARCHMONT, NY 10538 USA |
| Subject Category: Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental |
| IDS Number: 515ML |
| ISSN: 1043-0342 |
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