Temporally regulated expression patterns following in utero adenovirus-mediated gene transfer

Developmental patterns of gene expression were determined following intrava scular administration of adenovirus in utero, during sequential stages of m urine development Replication-deficient adenovirus (AdCMV.LacZ) was injecte d into yolk sac vessels of mouse embryos 12, 13, 15 and 18 days post-concep tion (d.p.c.). beta-Galactosidase (beta-gal) expression was evaluated 24-48 h after injection, at birth, and 5 weeks following normal delivery. Gene e xpression was defected in myocardial cells, endothelial cells of heart, lun g, kidney, adrenal, gut, and in hepatocytes. of expression were distinct fo r each stage of virus administration and time-point of analysis. of individ ual organ expression varied with injection time-point, with the largest num ber of organs expressing the transgene when embryos were injected at 15 d.p .c. beta-Gal activity was detected in only a subset of cells expressing the murine coxsackievirus and adenovirus receptor (CAR), indicating factors ot her than receptor distribution were responsible for the pattern of transgen e expression observed. These studies begin to define critical parameters af fecting intravascular gene delivery in utero and indicate that intrinsic de velopmental regulatory mechanisms may control exogenous gene expression. In travenous administration of adenovirus provides a unique approach for in ut ero gene transduction and will be a useful adjunct in evaluating genes whic h have early lethal mutations.