Artificial viruses and their application to gene delivery. Size-controlled gene coating with glycocluster nanoparticles.
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.
Aoyama
Yasuhiro
Y
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. aoyamay@sbchem.kyoto-u.ac.jp
Kanamori
Takuya
T
Nakai
Takashi
T
Sasaki
Toshinori
T
Horiuchi
Shohei
S
Sando
Shinsuke
S
Niidome
Takuro
T
D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics; D006027:Glycosides / Q000737:chemistry*; D008823:Micelles; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D011134:Polysaccharides / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D014780:Viruses / Q000737:chemistry*
D006027:Glycosides; D008823:Micelles; D011134:Polysaccharides; D004247:DNA