Fig. 2
AAV-delivered circ-arRNAs facilitate highly efficient and safe RNA editing in non-human primates. A Diagram of the dosing schedule and sampling process. Cynomolgus monkeys were administered a one-time injection of AAV8 at three specified dosage levels. Liver biopsies were collected on the marked days, and monkeys were euthanized for comprehensive liver analysis at the specified times. B Editing efficiency in PPIA transcripts in biopsy samples at varying dosage levels at week two; n = 3, technical replicates, mean ± SD. C Editing efficiency and RNAscope scores in five distinct liver lobes were assessed by RNAscope at various dosage levels. Each dot represents data from a single liver lobe; mean ± SD. D Vector copy numbers in five different liver lobes measured by qPCR at different dosage levels. Each dot represents data from a single liver lobe; mean ± SD. E Editing efficiency of PPIA transcripts in five different liver lobes determined by NGS at varying dosage levels. Each dot represents data from a single lobe of the liver; mean ± SD. F Correlation between editing efficiency and circ-arRNA abundance across the three dosage groups. Each dot signifies data from a single liver lobe; mean ± SD. G Editing efficiency of PPIA transcripts at various time points in monkeys that received a single injection of AAV8 at 3 × 1013 vg/kg. Liver biopsies were collected at weeks 2 and 4, and monkeys were euthanized for comprehensive liver analysis at week 13. For biopsy samples at weeks 2 and week 4, n = 3, technical replicates, mean ± SD. For the week 13 sample, each dot represents data from a single liver lobe; mean ± SD. H ALT and AST levels post-AAV8 administration. The yellow areas indicate the typical range for healthy non-human primates. The control group consisted of cynomolgus monkey injected only with normal saline. Student’s T test was used for all statistical comparisons between treatment and control groups. The control group comprised two non-human primates, and each treatment group contained one non-human primate