Single-turnover kinetic analysis of non-long terminal repeat retrotransposition defines the pathway and rate constants leading to second-strand synthesis

Site-specific non-long terminal repeat (non-LTR) retrotransposon-mediated gene therapy has the potential to revolutionize medicine by allowing insertion of large gene cargos at specific sites in a genome. Despite decades of effort, the reaction sequence of these elements remains to be fully elucidated, limiting the ability to engineer improved activity for gene insertion. One major question concerns whether the element-encoded protein is capable of synthesizing the second strand of the integrati