Patent Evaluation: Growth Inhibition by Oligonucleotides

Summary

Novelty: Synthetic oligonucleotides are claimed which comprise an RNA binding sequence or sequences which correspond to the site bound by the HIV protein tat, and which are capable of binding to tat within cells. These compounds have potential utility in therapy, since such binding may cause growth inhibition.

Biology: Autoradiographs show discrete complex formation between tat and ³²P-labelled RNA transcripts of HIV-1 TAR, HIV-2 TAR, SSA, ASS and G toll (loop). Filter binding assays are described, for example, HIV TAR (UVV) showed D_1/2 of 64 nM.

Chemistry: The preparation of tat protein, of TAR RNA and the chemical synthesis of oligoribonucleotides are all described. Preferred oligonucleotides comprise three unpaired residues which include a uridine residue corresponding to U₂₃ in the sequence HIV TAR RNA, as well as flanking base pairs corresponding to C₂₆—C₃₉ in the same sequence.