CORE--ANIMAL MODEL AND DELIVERY

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications & trials

Abstract

Description: (Taken directly from the application) Five of the pilot projects in the current application, and ten investigators with funded RO1s or other grants for gene transfer, have indicated a need for assistance with 1) instillation or aerosolization of gene delivery vehicles, 2) detection of reporter transgenes, 3) ion transport measurements in CF mice, or 4) histopathology in order to test safety and biologic effect of gene transfer to mammalian airways. The purpose of this core is to provide that expertise in a central, standardized fashion. The Core will process murine lungs for reporter gene activity (including luciferase, chloramphenicol acetyltransferase (CAT), and LacZ). We will also develop and test a new, highly sensitive reporter construct ($ -lactamase) for activity in vivo. Nasal potential difference measurements will be performed before and after gene transfer to cystic fibrosis and normal mice. This assay will be designed to test for functional correction of cystic fibrosis defects after CFTR gene expression in vivo. Finally, we will provide expertise in histopathology, so that lungs treated with gene transfer vectors can be processed and sectioned for qualitative and quantitative analysis of the extent and duration of the host inflammatory responses. These core functions are designed to facilitate the transition from in vitro proof of concept trials to in vivo analyses of CF gene transfer. The protocols described here are a crucial aspect of the development of gene therapy in cystic fibrosis.