Fig. 5

Restoration of α-L-iduronidase activity in liver and brain through AAV-delivered circ-arRNA in humanized IDUA^W402X mouse model. A Diagram showing the dosing schedule and sampling. B Editing rate of IDUA^W402X transcripts in the CNS (left) and various organs (right) in humanized Hurler syndrome mice 6 weeks after AAV-PHP.eB injection; each white dot represents an independent biological replicate, mean ± SD. C Measurement of IDUA protein catalytic activity using a 4-methylumbelliferyl IDUA substrate in the CNS (left), various organs (middle), and serum (right); each white dot represents an independent biological replicate, mean ± SD. D GAG content in tissues from the CNS (left) and various organs (right) 6 weeks post-AAV-PHP.eB infection; each white dot represents a biological replicate, mean ± SD. E NGS results showing bystander editing of IDUA^W402X transcripts in different brain regions 6 weeks after AAV-PHP.eB infection; asterisks represent synonymous mutation; n ≥ 2. F Hematoxylin–eosin staining of mice livers in different groups. Scale bar = 50 μm. Red arrows indicate foamy macrophages in the tissue due to GAG accumulation. Student’s T-test was used for all statistical comparisons between treatment and control groups