Caecum: A potential site for studying gene transfer in vivo

Over the past years we have designed and synthesized a new class of synthet ic vectors called phosphonolipids and then shown their ability to transfect lungs cells of mice with efficiency. One of them, GLB73, gave high levels of transfection. In the study reported here, we explored the potential of c aecum as an alternative site for studying the feasibility of gene transfer in this site. Transfections were performed by using two reporter genes enco ding for beta galactosidase and luciferase; transfection activity was asses sed using two tests: chemiluminescent and cytofluorimetric assays. The resu lts obtained showed successful gene transfer into the caecum: up to 27% cel ls were LacZ+ with a mean of 11%; the maximum of efficiency was also observ ed 3 days after transfection which then decreased until day 7. Our lipoplex was 8-fold more efficient than the naked DNA (Mann Whitney test; p = 0.03) . Moreover, we were able to visually follow the uptake of lipoplexes by ent erocytes from 30 mn to 3 days post transfection. So, this study constituted an encouraging first step in the assessment of t he caecum as a potential model for gene transfer. In the near future, furth er electrophysiological studies using the gene of interest, as CFTR gene sh ould be performed in the caecum.