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Problem Addressed

Both viruses and cancers have relatively high rates of mutation, which facilitates rapid evolution of drug tolerance. However, there mutational burden is a delicate balance, and viruses and cancer cells need to sustain a mutation rate and that is favorable for evolution, while also maintaining genetic stability. Too high of a mutational burden can lead to catastrophic collapse of genetic integrity and complete loss of virus or cell viability known as “lethal mutagenesis.” Lethal hypermutation has therefore been proposed as an anti-viral and cancer therapeutic technique and there is at least one FDA approved drug, ribavirin, that uses lethal mutagenesis to treat hepatitis C and viral hemorrhagic fever. The pro-drug KP1212 is another example of a promising mutagenic drug candidate, however, KP1212 displayed only marginal anti-viral effects in clinical trials. This technology is a method for increasing the mutagenicity of nucleoside analogs to potentially maximize their therapeutic potential.