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- Title
Adenovirus Gene Transfer to Amelogenesis Imperfecta Ameloblast-Like Cells.
- Authors
Borovjagin, Anton V.; Dong, Juan; Passineau, Michael J.; Ren, Changchun; Lamani, Ejvis; Mamaeva, Olga A.; Wu, Hongju; Keyser, Enid; Murakami, Miho; Chen, Shuo; MacDougall, Mary
- Abstract
To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3) fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold) of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both αvβ3/αvβ5 integrins and heparan sulfate proteoglycans (HSPGs) highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.
- Subjects
ADENOVIRUSES; GENETIC transformation; AMELOGENESIS imperfecta; AMELOBLASTS; CELL populations; ALKALINE phosphatase; COXSACKIEVIRUS diseases
- Publication
PLoS ONE, 2011, Vol 6, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0024281