Properties and Anti-Hiv Activity of Hairpin Antisense Oligonucleotides Containing 2′-Methoxynucleosides with Base-Pairing in the Stem Region at the 3′-End

A new type of hairpin antisense oligodeoxyribo-nucleotide, containing 2′-methoxynucleosides with base-pairing in the stem region at the 3′-end, was tested for 3′-exonuclease resistance and anti-HIV activity. An increased resistance to nuclease degradation has been observed by incubation of the hairpin oligo-nucleotides with DNA polymerase and foetal bovine serum. Of particular interest is the hairpin antisense oligonucleotide containing 2′-methoxynucleosides with base-pairing in the stem region at the 3′-end, which has increased nuclease resistance and hybridizes effectively with a complementary RNA. Furthermore, these compounds were assayed for inhibition of virus replication in HIV-1 infected MT-4 cells. In the anti-HIV activity test, the hairpin oligonucleotide phosphorothioate derivatives showed higher anti-HIV activities compared to their linear counterparts.