Destabilisation of viral quasi-species distributions - avoiding resistance phenomena

摘要

Destabilising viral quasi-species distributions while avoiding resistance phenomena by replication of the nucleic acids of the viruses in the distribution by means of a defective replication system, (a) where the defective replication system has a greater nucleotide miscopy rate than the viral wild-type replication system and where the viruses are replicated at least as efficiently by the replication system with the higher miscopy rate as by the replication system of the wild-type virus, (b) and/or negatively affecting the replication of the consensus sequence (nucleic acid sequence of the wild-type virus) in relation to other replicable nucleic acids. Pref. the replication systems are RNA or DNA polymerases or their cofactors. The defective replication of the viral nucleic acids may be induced by a chemical substance, esp. an antimetabolite or an allosteric effector of the replication system. Alternatively, the defective replication system may be a variant of a natural mutant spectrum of the quasi-species or a mutant produced by mutagenesis.