Systemic administration of AAV‐DNase I mediates liver expression and secretion of DNase I in vivo. (A) Gene expression of DNase I in AAV vector‐injected liver. Livers were isolated at 21 days from AAV‐DNase I group and total RNA was extracted. n = 3 mice/group. Data were analyzed by Welch's t‐test. (B, C) DNase I secretion from AAV‐DNase I‐treated mice after MC38 injection. AAV‐DNase I was systemically administered through the tail vein 4 days after MC38 injection. On day 17 after AAV‐DNase treatment, the levels of DNase I were significantly higher than levels before AAV‐DNase I injection and daily DNase I IP‐injected group in tumor‐bearing mice. n = 5 mice/group. Data were analyzed by two‐way ANOVA and Student's t‐test. (D, E, F, and G) The levels of hepatocellular injury and cholestasis markers (ALT, AST, ALP, TBIL). AAV‐DNase I did not increase markers of liver injury in wild‐type mice. n = 4 mice/group. Data were analyzed by Student's t‐test. All data represent mean ± SD. *P < 0.05, ***P < 0.001, ****P < 0.0001.