Artificial viruses and their application to gene delivery. Size-controlled gene coating with glycocluster nanoparticles

Abstract

Number- and size-controlled macromolecular associations are common in biology with viruses as a typical example. We report here a novel example of artificial viruses, in which the double-helical DNA is coated with 4-nm sized neutral glycocluster nanoparticles (GNPs) with a coating stoichiometry of approximately 2 GNPs per helical pitch (10 base pairs), where GNP arises from micellization of a cone-shaped, quadruple-chain glycocluster amphiphile having eight saccharide moieties with beta-glucoside termini on the calix[4]resorcarene macrocycle. The resulting "glycoviruses" are compactly packed (54 nm in the case of 7040 base-pair plasmid pCMVluc), are well charge-shielded (zeta congruent with approximately 0 mV), and effectively transfect cell cultures without notable cytotoxicity. The use of artificial viral vectors thus allows a new (nonamine/noncationic/nonpolymeric) access to gene delivery, a potential but still tough subject which has been studied extensively over the last 15 years by using viral or amine-based cationic vectors. The remarkable adhesion-manipulation ability of saccharide clusters also provides a strategy of bottom-up construction of nanometric or mesoscopic sizes.