Rahul Sharma1, Stephen F. Konieczny2, and You-Yeon Won1. (1) School of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette, IN 47907, (2) Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907
Efficient transport of the injected DNA to specific sites in the body is the key requirement for delivering therapeutic dosage of curative DNA to diseased cells. In order to meet this requirement we need a gene carrier that can maintain high levels of the encapsulated DNA during circulation and target the diseased cells with high specificity. To this end we have developed a new class of gene carriers (“micelleplexes”) by complexation of positively charged micelles of a novel ABC triblock copolymer with DNA. Ex vivo characterization of the micelleplexes suggest that they are more suitable for attaining long term DNA circulation in vivo than conventional polymer-based gene carriers. In this talk we will first present recent pharmacokinetics studies performed in mice using the micelleplexes to directly evaluate this prediction. Our results show that the micelleplexes are indeed able to circulate high levels of intact DNA for long durations under physiological conditions. We will also present results of in vitro transfection studies performed in mammalian cell-lines using micelleplexes to study the effect of attached ligands on their surface on the expression of the encapsulated DNA. We find that while the expression remains extremely low in the absence of attached ligands, it increases dramatically upon incorporation of suitable ligands. These findings suggest that the non-specific uptake of micelleplexes during circulation in the body is expected to be very low, and highly specific targeted delivery of the encapsulated DNA can be achieved by attachment of ligands. Taken together these results establish the immense potential of the micelleplexes as DNA carriers for targeted in vivo delivery.