Journal
MOLECULAR THERAPY
Volume 10, Issue 3, Pages 500-506Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2004.05.032
Keywords
gene transfer; airway epithelia; adenovirus; EPO; erythropoietin; CAR
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Funding
- NHLBI NIH HHS [HL51670-10] Funding Source: Medline
- NIDDK NIH HHS [DK54759] Funding Source: Medline
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In well-differentiated human airway epithelia, the coxsackie B and adenovirus types 2 and 5 receptor (CAR) resides on the basolateral membrane. Replacing the transmembrane and cytoplasmic tail of CAR with a glycosyl-phosphaticlylinositol anchor (GPI-CAR) allows apical localization of GPI-CAR, where it can bind adenovirus and enhance gene transfer in vitro. To test this hypothesis further and to investigate requirements and barriers we developed an in vivo model that quantitatively assesses gene transfer of erythropoietin (EPO) to mouse airway epithelia. Our data suggest that erythropoietin is secreted basolaterally, allowing possible access to the bloodstream. The data also suggest that basolateral adenovirus-mediated airway epithelia EPO secretion persists for long periods and could be used to study persistence in vivo. Additionally, the increase in hernatocrit in response to the increased serum EPO could be used for therapeutic purposes. Finally, we tested the ability of apically localized CAR to enhance the infection of AdEPO in mouse airway epithelia in vivo. The data suggest that apical receptors in airway epithelia may be sufficient to improve adenovinus infection of airway epithelia in vivo.
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