Efficient cytosolic delivery of antisense oligonucleotides using listeriolysin o-containing liposomes

摘要

Nucleic acid-based therapy provides powerful solutions to many enduring medical problems. Prior to the achievement of their full therapeutic efficacy and the launching of nucleic acid=based drugs, an effective delivery system must be formulated to overcome the barriers in delivering these drugs to their cellular and subcellular targets. The effective use of antisense oligonucleotides is limited particularly by the membrane barrier that prevents necessary concentrations of the drug to access its site of action in the cytosol and nucleus. for efficient cytosolic delivery of intact antisense oligonucleotides, we have developed liposomes containing listeriolysin O (LLO) as a delivery vehicle. These "listeriosomes" utilize the endosomolytic properties of LLO, the bacterial hemolysin from Listeria monocytogenes, to mediate the escape of the drug from the endosome into the cytosol and nucleus, avoiding lysosomal degradation.