Kabanov A V, Vinogradov S V, Suzdaltseva Y G
Moscow Institute of Biotechnology, Inc., Faculty of Chemistry, Moscow State University, Vorobievy Gory, Russia.
Bioconjug Chem. 1995 Nov-Dec;6(6):639-43. doi: 10.1021/bc00036a001.
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 virus reproduction.
由聚氧乙烯（PEO）链和聚精胺（PS）链组成的水溶性嵌段共聚物载体已被开发用于将反义寡核苷酸（oligo）递送至靶细胞。这些共聚物在水溶液中能自发地与寡核苷酸形成复合物。PS嵌段通过静电作用与寡核苷酸结合，从而提高了寡核苷酸的稳定性。同样，极性的PEO嵌段赋予了复合物水溶性。本文（i）报道了二嵌段PEO-PS共聚物的合成，（ii）评估了该共聚物与磷酸二酯寡核苷酸（与单纯疱疹病毒1型立即早期前体mRNA 4和5的剪接位点互补）形成的复合物对该病毒在Vero细胞中繁殖的影响。感染后22小时和39小时的感染滴度数据表明，共聚物-寡核苷酸复合物对病毒繁殖的抑制作用超出了检测限。相反，游离寡核苷酸仅在感染后22小时抑制病毒繁殖，而在感染后39小时观察到显著的病毒滴度。本研究结果表明，共聚物复合物增强了寡核苷酸对病毒繁殖的序列特异性抑制作用。
