Disclosed are compositions comprising mutant chondroitinase ABC I and methods of their use. Compositions comprising either the nucleic acid or amino acid sequence of mutant chondroitinase ABC I are disclose. Specifically, compositions comprising the nucleic acid sequence of SEQ ID NO:2 or the amino acid sequence of SEQ ID NO:6 are disclosed. The mutant chondroitinase ABC I compositions can be used to treat cancer, increase oncolytic virus spread or treat central nervous system injury.