Antisense strategies for oncogene inactivation

C. A. Stein, Luba Benimetskaya, S. Mani

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Antisense oligonucleotides have been evaluated as antineoplastic agents in a series of clinical trials, with mixed results. However, phase III trials incorporating G3139, a phosphorothioate oligomer targeted to the initiation codon region of the bcl-2 mRNA, have recently been completed in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL). This article discusses the mechanism of the antisense effect and its dependence on the cellular internalization of oligonucleotides and the activity of RNase H. It also describes the properties, specific and nonspecific, of phosphorothioate oligonucleotides, the predominant species in current clinical trials, and discusses pharmacokinetic data obtained from earlier phase I and II trials employing these molecules. While the application of antisense technology to the treatment of human cancer is conceptually straightforward, in practice there are many complicated, mechanistically based questions that must be considered.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalSeminars in oncology
Issue number6
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Hematology
  • Oncology


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