WATER-SOLUBLE BLOCK POLYCATIONS AS CARRIERS FOR OLIGONUCLEOTIDE DELIVERY

Water-soluble, block copolymeric carriers consisting of polyoxyethylen e (PEG) and polyspermine (PS) chains have been developed for the deliv ery of antisense oligonucleotides (oligo) into the target cells. These copolymers spontaneously form complexes with oligos in aqueous soluti ons. The PS block electrostatically binds to the oligo, and as a resul t, the stability of the oligo is increased. Similarly, the polar PEO b lock provides for the aqueous solubility of the complex. This paper (i ) reports the synthesis of the diblock PEO-PS copolymer and (ii) evalu ates the effects of the complexes formed between this copolymer and ph osphodiester oligo, complementary to the splice junction of herpes sim plex virus type 1 immediate early pre-mRNAs 4 and 5, on the reproducti on of this virus in Vero cells. Infectious titer data 22 and 39 h post infection indicates that the copolymer-oligo complex inhibits the rep roduction of the virus beyond the detection limit. Conversely, the fre e oligo inhibits the reproduction of the virus only 22 h postinfection , while 39 h postinfection significant virus titers are observed. The results of this study suggest that the copolymeric complex increases t he sequence-specific inhibition effect of oligo on the virus reproduct ion.