Oligo-targeting for editing and profiling drug-resistant drug-targets in parasitic trypanosomatids

Several new drugs, with known targets, are in clinical development against sleeping sickness, Chagas disease or leishmaniasis, but our understanding of resistance-associated mutations remains incomplete. We report the development of oligo-targeting for templated precision editing of these priority drug-targets. The outputs provide confirmation of on-target activity, reveal multiple distinct mutations at the same site that can yield drug-resistance, and facilitate rapid assessment of potential impacts on anti-parasite drug efficacy.