Kinetic selection of HPV 16 E6/E7-directed antisense nucleic acids: Anti-proliferative effects on HPV 16-transformed cells

Francesca Venturini, Joris Braspenning, Matthias Homann, Lutz Gissmann, Georg Sczakiel*

*Corresponding author for this work
    54 Citations (Scopus)

    Abstract

    The E6/E7-coding sequences of the human papillomavirus type 16 (HPV 16) were probed for kinetic accessibility in vitro by pools of catalytic antisense RNA. Only long-chain complementary RNA and very few antisense sequences with a 3' portion complementary to a 10 nt window within unspliced and spliced E6-coding target sequences showed fast annealing with k(ass) values of up to 104 M-1s-1 indicating that the majority of E6/E7 RNA sequences are unfavourable targets for antisense inhibitors and ribozymes. Fast-annealing antisense oligodeoxyribonucleotides directed against the window of 10 nt inhibited cell proliferation of HPV 16-transformed SiHa cells but not slow-annealing antisense species. Antisense RNA of several hundred nucleotides in length also showed significant antiproliferative activity. Biological effects of antisense oligodeoxyribonucleotides were specific for the antisense sequence, could only be found in HPV-positive but not in HPV-negative cell lines, and were related to decreased levels of E7 protein and E6/E7-specific transcripts. This work suggests that HPV 16 E7/E6 sequences exhibit a low accessibility for antisense oligonucleotides. This can be overcome, however, by exploiting the relationship between fast annealing of antisense species and their increased efficacy in human cells.

    Original languageEnglish
    JournalNucleic Acids Research
    Volume27
    Issue number7
    Pages (from-to)1585-1592
    Number of pages8
    ISSN0305-1048
    DOIs
    Publication statusPublished - 01.04.1999

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