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RNA viruses are a significant source of morbidity and mortality in humans every year. Additionally, the potential use of these viruses in acts of bioterrorism poses a threat to national security. Given the paucity of vaccines or postexposure therapeutics for many highly pathogenic RNA viruses, novel treatments are badly needed. Sequence-based drug design, under development for almost 20 years, is proving effective in animal models and has moved into clinical trials. Important advances in the field include the characterization of RNA interference in mammalian cells and chemical modifications that can dramatically increase the in vivo stability of therapeutic oligonucleotides. Antisense strategies utilize single-stranded DNA oligonucleotides that inhibit protein production by mediating the catalytic degradation of target mRNA, or by binding to sites on mRNA essential for translation. Double-stranded RNA oligonucleotides, known as short-interfering RNAs (siRNAs), also mediate the catalytic degradation of complementary mRNAs. As RNA virus infection is predicated on the delivery, replication, and translation of viral RNA, these pathogens present an obvious target for the rapidly advancing field of sequence-specific therapeutics. Antisense oligonucleotides or siRNAs can be designed to target the viral RNA genome or viral transcripts. This article reviews current knowledge on therapeutic applications of antisense and RNA interference for highly pathogenic RNA viral infections.

Book chapter by Michael L Riordan, the founder and CEO of Gilead Sciences, on Antisense Technology, Oligonucleotides, Triple Helix, Genetic Targeting. Chapter title: Genetic Targeting: The Third Wave in Therapeutic Development. In "Advances in Applied Biotechnology Series Volume 2: Discoveries in Antisense Nucleic Acids," Christine L Brakel, Editor. 1989.

Book chapter by Michael L Riordan, the founder and CEO of Gilead Sciences, on Antisense Technology, Oligonucleotides, Triple Helix, Genetic Targeting. Chapter title: Genetic Targeting: The Third Wave in Therapeutic Development. In "Advances in Applied Biotechnology Series Volume 2: Discoveries in Antisense Nucleic Acids," Christine L Brakel, Editor. 1989.

In order to define mechanisms by which HER2/neu overexpression drives breast cancer cell growth and chemoresistance, antisense oligodeoxynucleotides (ODNs) have been used to down-regulate HER2/neu expression in human breast cancer cells. Such antisense ODNs suppress HER2/neu mRNA and protein expression in a dose-dependent, sequence-specific manner. Antisense ODN-mediated down-regulation of HER2/neu expression in HER2/neu- overexpressing breast cancer cells inhibits cell cycle progression in GO/GI and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2/neu overexpressing breast cancer cells with HER2/neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cell growth and activation of apoptosis. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with HER2/neu antisense ODNs and chemotherapeutic agents in breast cancer xenografts in nude mice.