A novel hybrid adenoretroviral vector with more extensive E3 deletion extends transgene expression in submandibular glands.
Hum Gene Ther Methods
; 23(3): 169-81, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22817829
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glándula Submandibular
/
Terapia Genética
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Adenoviridae
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Eritropoyetina
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Técnicas de Transferencia de Gen
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Transgenes
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Vectores Genéticos
Tipo de estudio:
Evaluation_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Hum Gene Ther Methods
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos