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CIRCLE-seq with genomic DNA from CD46/B-YAC mice and sgHBG#2 RNA plus recombinant SpCas9 272 potential off-target sites (OTS) NGS for top 20 OTS 80: === non-transduced I mee HOALEF 1a ABEBe UTI 0.20 0.15: 0.10: 0.050.00: FAA ARP TARR ARRS TRAE ARS ARS FAARARS TARRY AR AAR On-target_ mOTS1 mOTS2 mOTS3 mOTS4 mOTSS mOTS6 mOTS7 mOTS8 mOTS9 mOTS10 80: 60: 40: 20: 0.20 0.15 0.10 oan AAR PHAR AAR ARS FAAS PARITY PAR ARH PAAR HAR mOTS11 mOTS12_ mOTS13 mOTS14 MOTS15 mOTS16 mOTS17 mOTS18 mOTS19 mOTS20 1.0 0.5: 0.20 8 015 0.10. 8 O05 '6 we 0.00 % of reads containing A>G conversions A>G conversions % of reads containing taining indels , ay ON > nO OO KL 1D LEBER OEBLEB BSN IE MPEP PLLC SSP CCL OES Fig.9