FUSOGENIC PROPERTIES OF SENDAI VIROSOME ENVELOPES IN RAT-BRAIN PREPARATIONS

Sendai virosomes were characterized with respect to their ability to b ind to, fuse with, and introduce substances into several rat brain pre parations. Encapsulation efficiency for Sendai virosomes was enhanced but binding to cerebral cortical P2 preparations was attenuated by add ition of bovine brain phosphatidylcholine during reconstitution. A hig her percentage of Sendai virosomes than phosphatidylcholine liposomes appeared to bind to, fuse with and subsequently deliver [C-14]sucrose into osmotically labile pools of the P2 preparation. Fusogenic activit y was estimated by measuring dequenching of fluorescently labelled N-N BD-phosphatidylethanolamine. More virosomally encapsulated [C-14]sucro se was bound to the P2 fraction than introduced into osmotically labil e organelles, and the fraction of vesicles undergoing fusion was inter mediate between these two values. Non-encapsulated [C-14]sucrose did n ot bind to and was not taken up by the P2 fraction in a quantifiable m anner. Virosomal envelopes also bound to primary cultures of rat brain neurons and glia in an apparently saturable manner. Addition of incre asing amounts of the adenoassociated virus-derived vector pJDT95 incre ased encapsulation efficiency, and virosomes reconstituted in the pres ence of 60 mug DNA retained most of their binding activity (5.4% of to tal label) compared to those containing [C-14]sucrose alone (8.4%). Th ese data indicate that Sendai virosomes may be useful in the delivery of substances into brain-derived tissues, potentially for the modulati on of gene expression and neurotransmission.