PMID: 8608176Nov 1, 1995Paper

Water-soluble block polycations as carriers for oligonucleotide delivery

Bioconjugate Chemistry
A V Kabanov Alakhov VYu

Abstract

Water-soluble, block copolymeric carriers consisting of polyoxyethylene (PEO) and polyspermine (PS) chains have been developed for the delivery of antisense oligonucleotides (oligo) into the target cells. These copolymers spontaneously form complexes with oligos in aqueous solutions. The PS block electrostatically binds to the oligo, and as a result, the stability of the oligo is increased. Similarly, the polar PEO block provides for the aqueous solubility of the complex. This paper (i) reports the synthesis of the diblock PEO-PS copolymer and (ii) evaluates the effects of the complexes formed between this copolymer and phosphodiester oligo, complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5, on the reproduction of this virus in Vero cells. Infectious titer data 22 and 39 h post infection indicates that the copolymer-oligo complex inhibits the reproduction of the virus beyond the detection limit. Conversely, the free 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 copolymer complex increases the sequence-specific inhibition effect of oligo on the viru...Continue Reading

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