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Currently, there is no anti-viral therapeutic available against JCPyV infection. The clustered regularly interspaced short palindromic repeat (CRISPR)\/CRISPR-associated protein 9 (Cas9) system (CRISPR\/Cas9) is a genome editing tool capable of introducing sequence specific breaks in double stranded DNA. Here we show that the CRISPR\/Cas9 system can restrict the JCPyV life cycle in cultured cells. We utilized CRISPR\/Cas9 to target the noncoding control region and the late gene open reading frame of the JCPyV genome. 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