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Updated: Sep 29, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
Inhibition of human immunodeficiency virus type 1 replication by P-stereodefined oligo(nucleoside phosphorothioate)s
Takubumi Inagawa1, Hideki Nakashima, Boleslaw Karwowski
1Department of Industrial Chemistry, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Japan.
Abstract:
Oligo(nucleoside phosphorothioate)s (S-ODNs), if prepared by conventional methods, consist of a mixture of diastereomers by virtue of the asymmetry of the phosphorus atom involved in the internucleotide linkages. This may affect the stability of the complexes formed between S-ODNs and complementary oligoribonucleotides, which is commonly accepted as the most important factor in determining the efficacy of an antisense approach. Using HIV-1-infected MOLT-4 cells via a long-term culture approach, we studied the influence of the P-chirality sense of stereodefined 28mer oligo(nucleoside phosphorothioate)s, [All-Rp]-S-ODN-gag-28-AUG and [All-Sp]-S-ODN-gag-28-AUG, complementary to the sequence starting at the AUG initiation codon of the gag mRNA of HIV-1, upon the anti-HIV-1 activity. The [All-Sp]-S-ODN-gag-28-AUG at a low concentration of 0.5 microM can completely suppress HIV-1(gag) p24 antigen expression in HIV-1-infected MOLT-4 clone 8 cells for 32 days. Cells treated with [All-Rp]-S-ODN-gag-28-AUG (0.5 microM) showed a high level of the antigen expression at day 16. Furthermore, satisfactory suppression could not be achieved from a random [Mix]-S-ODN-gag-28-AUG, consisting of a diastereomeric mixture of the oligonucleotides. Our results suggest that chemotherapy based upon the use of stereodefined antisense [All-Sp] S-ODN may be a more effective method for reducing the viral burden in HIV-1-infected individuals.
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