Cytotoxic hammerhead ribozymes

Ruth Levitz, Yuzhi Dong, Jian Ying Wang, Sheau Wen Jeng, Chang Rung Chen, Jing Wa Wang, Xilin Zhao, Jianfeng Zhou, Tao Lu, Karl Drlica

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Small catalytic RNA molecules of the hammerhead ribozyme type were found to have cytotoxic effects unrelated to their intended activity. An expression library of ribozyme sequence variants was constructed in a recA-deficient strain of Escherichia coli such that individual library members differed in regions designed to form base pairs with human immunodeficiency virus-1 (HIV-1) tat mRNA. The parental ribozyme and many variants exhibited a bacteriostatic effect. One variant studied in detail was also bactericidal. When its expression was induced, ribozyme-dependent inhibition of bacterial growth was not observed in recA+ or recA+ lexA3 (Ind-) cells, suggesting that the recombination function of the RecA protein, not the absence of the SOS response, is sufficient to alleviate the cytotoxic effect. These data document the need for careful testing for toxic effects during intracellular studies of ribozyme action.

Original languageEnglish (US)
Pages (from-to)117-123
Number of pages7
JournalAntisense and Nucleic Acid Drug Development
Volume9
Issue number2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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    Levitz, R., Dong, Y., Wang, J. Y., Jeng, S. W., Chen, C. R., Wang, J. W., Zhao, X., Zhou, J., Lu, T., & Drlica, K. (1999). Cytotoxic hammerhead ribozymes. Antisense and Nucleic Acid Drug Development, 9(2), 117-123. https://doi.org/10.1089/oli.1.1999.9.117