A majority of viruses afflicting humans and livestock have RNA genomes which are believed to exist in a duplex A conformation during replication. Such long A-form duplexes, which have been characterized at atomic resolution, are unique to virus infected cells (uninfected cells have only short A-form structures) and therefore offer excellent well-characterized targets for prospective antiviral agents.To exploit these virus-specific targets, synthetic polymers have been devised which are designed to inactivate selected A-form duplexes without concommitant attack on the Bform duplexes comprising the infected organism's genome. Calculations suggest that a single such A-directed anti-gene may be ef f ective against most or all RNA viruses.The Phase I effort will be continuation of a proof-of-concept study which includes: a) assembly of a series of simple prototype anti-genes, b) assessment of their strength and specificity of binding to both target and nontarget poly-nucleotides, and c) assessment of the biological consequences of such binding.The expectation is that these prototype anti-genes will be found to bind to their specific target duplexes but not to polynucleotides differing in sequence or conformation, and that such binding will render the target sequences genetically inactive. Such a result will verify that the predicted molecular interactions occur with the requisite form and sequence specificities - thereby laying a rigorous foundation for subsequent development of an A anti-gene designed for use against a broad range of RNA viruses.Based on its expected efficacy against such diseases as measles, mumps, polio, rabies, hepatitus A, AIDS, most flu and colds, and a wide range of economically important afflictions in livestock, it is projected that a safe and effective broad-spectrum RNAdirected anti-gene will have an annual world market well in excess of $4 billion.National Cancer Institute
