Daily dosing of GalNAc- and mannose-conjugated anti-MARV siRNA reduced MARV-induced mortality in guinea pig
Guinea pigs (n = 5 for conjugate treatment group, n = 1 for untreated group) were challenged with a lethal dose of MARV Angola strain. Twenty-four hours post viral exposure, animals were subcutaneously injected with unconjugated siMARV, tetra-GalNAc-siMARV, hexa-mannose-siMARV alone, combination of tetra-GalNAc-siMARV + hexa-mannose-siMARV (1:1) (10 mg/kg total siRNA, mixed in one vial; daily dosing, seven doses). In one group, treatment of tetra-GalNAc-siMARV + hexa-mannose-siMARV (1:1) (10 mg/kg total siRNA, mixed in one vial; daily dosing, seven doses) was immediately followed with GalNAc-ERP + mannose-ERP (1:1) (10 mg/kg total ERP, mixed in one vial, single subcutaneous dose on the first day of conjugate treatment). The antiviral efficacy was evaluated by survival rates (A), viremia (B), and body weights (C). The error bars stand for standard error of mean (SEM).