Fig. 4

Optimization of the circ-arRNA for human IDUA^W402X mutation transcripts in cultured cells. A Diagram illustrating the human Hurler syndrome mouse model and corresponding reporter system. B–D The percentage of eGFP⁺ cells indicating the editing rate of various circ-arRNA designs targeting the reporter transcripts in HEK293T cells; n = 3, mean ± SD. E The percentage of eGFP⁺ cells and mean fluorescence intensity showing the editing rate of the reporter transcripts in HEK293T cells for 20 different versions of circ-arRNA; n = 3, mean ± SD. F NGS results showing the bystander editing for versions 5, 6, 7, 9, and 14 of circ-arRNA_85+C+15_AC30_3’; asterisks represent synonymous mutation; n = 3, mean ± SD. G Editing rate of IDUA^W402X transcripts in GM06214 cells 2 weeks post-AAV-PHP.eB infection; n = 2, mean ± SD. H Measurement of IDUA protein catalytic activity using a 4-methylumbelliferyl IDUA substrate in GM06214 cells 2 weeks post-AAV-PHP.eB infection; n = 2, mean ± SD. I NGS results showing the bystander editing of IDUA transcripts; asterisks represent synonymous mutations; n = 2, mean ± SD. Student’s T-test was used for all statistical comparisons between the different groups