title: A novel hybrid adenoretroviral vector with more extensive E3 deletion extends transgene expression in submandibular glands.
abstract: Salivary glands are an attractive target for gene transfer. Salivary epithelial cells are considered to be highly differentiated and have low rates of cell division (~6 months), affording the opportunity to obtain relatively long-term transgene expression in the absence of genomic integration. Here, we report a novel modified hybrid adenoretroviral vector, which provides stable transgene expression in salivary epithelial cells in vivo for up to 6 months in the absence of genomic integration. This modified hybrid vector, Ad(ΔE1/3)LTR(2)EF1α-hEPO, encodes human erythropoietin (hEPO) and differs from a previously developed hybrid vector, AdLTR(2)EF1α-hEPO, by having more extensive E3 gene deletion. Following direct salivary gland gene transfer by retroductal cannulation, rats transduced with Ad(ΔE1/3)LTR(2)EF1α-hEPO had sustained, elevated serum hEPO levels and hematocrits for 6 months (length of experiment), as compared with ~2 months for animals administered the AdLTR(2)EF1α-hEPO vector. Immunohistochemistry demonstrated that this novel vector could transduce both acinar and ductal cells. Interestingly, the Ad(ΔE1/3)LTR(2)EF1α-hEPO vector evoked much weaker local (salivary gland) immune responses than seen after AdLTR(2)EF1α-hEPO vector delivery, which likely permits its significantly lengthened transgene expression in this tissue.
authors: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. czheng@dir.nidcr.nih.gov
authors: Changyu
authors: C
authors: Zheng
authors: Ana P
authors: AP
authors: Cotrim
authors: Nikolay
authors: N
authors: Nikolov
authors: Fumi
authors: F
authors: Mineshiba
authors: William
authors: W
authors: Swaim
authors: Bruce J
authors: BJ
authors: Baum
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006400:Hematocrit; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics*; D014461:Ultracentrifugation
chemical_list: D017931:DNA Primers; D020648:Peptide Elongation Factor 1; D004921:Erythropoietin