TY - JOUR
T1 - Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application
AU - CAPUTO, A.
AU - BETTI, M.
AU - ALTAVILLA, G.
AU - BONACCORSI, A.
AU - BOARINI, C.
AU - MARCHISIO, M.
AU - BUTTÒ, S.
AU - SPARNACCI, Katia
AU - LAUS, Michele
AU - TONDELLI, L.
AU - ENSOLI, B.
N1 - Funding Information:
This work was supported by Italian grants from the Istituto Superiore di Sanità (AIDS Project 1999, and the Italian Concerted Action on HIV–AIDS Vaccine Development) and from the Associazione Nazionale per la lotta contro l’AIDS (ANLAIDS). We are grateful to M. Lanfredi for animal care, and I. Mantovani, C. Celeghini, S. Capitani (University of Ferrara) for excellent assistance at the fluorescence and confocal microscopes.
PY - 2002
Y1 - 2002
N2 - 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 a 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.
AB - 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 a 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.
UR - https://iris.uniupo.it/handle/11579/31256
U2 - 10.1016/S0264-410X(02)00099-3
DO - 10.1016/S0264-410X(02)00099-3
M3 - Article
SN - 0264-410X
VL - 20
SP - 2303
EP - 2317
JO - Vaccine
JF - Vaccine
IS - 17-18
ER -
