Reexpression following readministration of an adenoviral vector in adult mice after initial in utero adenoviral administration

Adenovirus-mediated gene delivery is limited by the induction of immune res ponses that produce toxicity and prevent reexpression. To determine whether adenoviral delivery in the preimmune fetus would produce tolerance, we ass essed luciferase (luc) expression following sequential pre- and postnatal a denoviral-mediated gene delivery. Day 15 fetuses were injected intrahepatic ally with 1 x 10(7) pfu of an adenoviral-luc vector (Ad-luc). Following in utero injection, hepatic luc expression persisted 1 month postnatally. No h umoral response to adenovirus or inc was detected. Adult mice, previously i njected in utero, were reinjected intravenously with 5 x 10(8) pfu of Ad-lu c at 3 months of age and again at 6 months with either 5 x 108 pfu of Ad-lu c or cationic liposome-DNA complexes (CLDC). Following the first postnatal injection, animals injected in utero had levels of luc comparable to those of age-matched naive controls. However, both control and experimental anima ls subsequently developed antibodies to adenovirus and inc. No further expr ession was achieved with a second postnatal injection of Ad-luc or with del ivery of CLDC-luc. These studies demonstrate that the delivery of adenovira l vectors in utero at E15 does not elicit an immune response. However, deli very of recombinant adenovirus postnatally results in brisk and limiting im mune responses regardless of the in utero exposure.