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[Preprint]. 2024 Jun 25:2024.06.20.599943. [Version 1] doi: 10.1101/2024.06.20.599943

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Fig 4. — (A) chemical modifications used to optimize di-siRNA^SOD_123. (B) chemical modifications and structure of original di-siRNA^SOD_123 (C) chemical modifications and structure of methyl-rich di-siRNA^SOD_123 (D) In vitro dose response of original (red) or methyl-rich (maroon) di-siRNA^SOD_123 (E) in vivo protein silencing of original or methyl-rich siRNA at two months post-injection. (F) Kaplan-Meier survival curve comparing G93A mice treated with the original or methyl-rich di-siRNA^SOD_123 or NTC control. (G) Chemical modifications and structure of original di-siRNA^SOD_123. (H) Chemical modifications and structure of di-siRNA^SOD_123 exNA (exNA noted with black arrows). (I) 7-point dose-response curves of original (red) or exNA (purple) di-siRNA^SOD_123 (J) Kaplan-Meier survival curve comparing G93A mice treated with the original or exNA di-siRNA^SOD_123 or NTC control. (K) Chemical modifications and structure of exNA di-siRNA^SOD_123 (PS noted with orange arrows, exNA with black arrows) (L) Chemical modifications and structure of exNA di-siRNA^SOD_123 with reduced phosphorothioate content (exNA noted with black arrows). (M) 7-point dose-response curves of exNA di-siRNA^SOD_123 high PS (purple) or exNA di-siRNA^SOD_123 low PS (teal). (N) Kaplan-Meier survival curve comparing G93A mice treated with exNA di-siRNA^SOD_123 high PS (purple), exNA di-siRNA^SOD_123 low PS, or standard NTC control. Survival studies used single injection at 6 weeks.