Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application.
A novel class of cationic block copolymers constituted by a neutral hydrophilic poly(ethylene glycol) (PEG) block and a positively charged poly(dimethylamino)ethyl methacrylate block was prepared for delivery of DNA. These block copolymers spontaneously assemble with DNA to give in aqueous medium micellar-like structures. Five of these novel block copolymers (K1-5), differing in the length of both the PEG chain and the linear charge density of the poly(dimethylamino)ethyl methacrylate block, were prepared and analyzed for gene delivery, gene expression and safety. All five block copolymers protected DNA from DNAse I digestion and delivered the DNA into the cell. However, only three of them (K1, K2 and K5) released the DNA at level allowing efficient gene expression into cells. No toxic effects of both the copolymers alone or their DNA complexes were observed in vitro or in mice. In addition, copolymers were scarcely immunogenic. These results indicate that this novel class of cationic block copolymers is safe and possesses the biological characteristics required for DNA delivery, thus, representing promising vehicles for DNA vaccination.
Caputo
Antonella
A
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy. cpa@unife.it
Betti
Monica
M
Altavilla
Giuseppe
G
Bonaccorsi
Angela
A
Boarini
Chiara
C
Marchisio
Marco
M
Buttò
Stefano
S
Sparnacci
Katia
K
Laus
Michele
M
Tondelli
Luisa
L
Ensoli
Barbara
B
D016915:AIDS Vaccines; D000818:Animals; D003850:Deoxyribonuclease I / Q000378:metabolism; D004337:Drug Carriers; D015870:Gene Expression; D015696:Gene Products, tat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009757:Nylons / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D019444:Vaccines, DNA; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004337:Drug Carriers; D015696:Gene Products, tat; D008689:Methacrylates; D008823:Micelles; D009757:Nylons; D019444:Vaccines, DNA; C109846:poly(2-(diethylamino)ethyl methacrylate); D054322:tat Gene Products, Human Immunodeficiency Virus; D011092:Polyethylene Glycols; D003850:Deoxyribonuclease I