EFFICIENT ADENOVIRAL-MEDIATED MURINE NEONATAL SMALL-INTESTINAL GENE-TRANSFER IS DEPENDENT ON ALPHA(V) INTEGRIN EXPRESSION

Background/Purpose: Clinical application of gene therapy for patients who have inflammatory bower disease or short bower syndrome will requi re the development of new strategies to improve the efficiency of smal l intestinal gene transfer. Previously, the authors developed a method for adenoviral-mediated small intestinal gene transfer in vivo in neo natal and adult mice. The present study evaluates the hypothesis that the integrins alpha(v) beta(3) and alpha(v) beta(5) the secondary rece ptors for adenoviral internalization, play a facilitative role in neon atal murine adenoviral-mediated small intestinal gene transfer. Method s: Immunohistochemical techniques identified the integrin alpha(v) bet a(3) and the integrin subcomponents alpha(v), beta(3), and beta(5) in neonatal and adult small intestine. The effects of integrin receptor a ntagonists on transgene expression was also studied in our neonatal mo del of adenoviral-mediated small intestinal gene transfer in vivo. Res ults: Gene transfer was significantly decreased by the addition of int egrin receptor antagonists versus control peptide. Integrin alpha(v) b eta(3) and integrin subcomponent alpha(v), beta(3) and beta(5) are exp ressed in neonatal and adult small intestine. Integrin antagonists adm inistered simultaneously blocked efficient adenoviral-mediated neonata l small intestinal gene transfer in vivo compared with control peptide . Conclusion: Strategies to upregulate integrin expression may improve adenoviral-mediated small intestinal gene transfer.