Studies on the use of nickase and nuclease inactive-Cas9 systems to target HBc protein-coding gene (hepatitis B core/capsid protein) for inhibition of hepatitis B virus (HBV) replication in vitro (HepG2.2.15.7, HepG2-hNTCP-C4, and Huh7 cells) and in vivo (mouse liver) have shown the efficient elimination of viral infection. Here, C4A is linked to viral infectious disease.