A majority of viruses afflicting vertebrates have RNA genomes which exist in a duplex A conformation during replication. Such A-form duplexes have a relatively uncomplicated structure which has been characterized at atomic resolution and, because long A-form structures are unique to virus-infected cells (uninfected cells have only very short A-form duplexes), such structures offer an excellent well characterized target for prospective antiviral agents. To exploit these virus-specific targets synthetic polymers have been devised which are designed to stabilize and thereby inactivate selected A-form duplexes without concommitant attack on the B-form duplexes comprising the infected organism's genome. Calculations suggest that a single A-directed anti-gene may be effective against essentially all RNA viruses. The ANTI-GENE DEVELOPMENT GROUP proposes herein support for 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 polynucleotides; and, c) assessment of the biological consequences of such binding. The expectation in this work 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 said target duplexes genetically inactive. Such a result will verify that the predicted molecular interactions occur with the requisite form and sequence specificity - thereby laying a rigorous foundation for subsequent development of broad-spectrum A anti-genes designed for therapeutic use against a wide range of RNA viruses.
