Cationic liposome conjugation to recombinant adenoviral vector reduces viral antigenicity

Adenoviral (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficacy of re peated vector administration. In this study, we demonstrated that conjugati on of Ad vector with our novel cationic liposomes could reduce viral antige nicity in vivo. Mice subcutaneously injected with liposome-conjugated Ad ve ctor showed a 6.5-fold reduction of anti-Ad antibodies with neutralizing ac tivity, compared to those with unconjugated Ad vector, Interestingly, we al so found that the conjugated vector is less susceptible to inactivation by neutralizing antibodies in vitro and in vivo. Our results suggest that lipo some conjugation reduces viral antigenicity, shields vectors from neutraliz ing antibody, and may allow repeated Ad vector administration.