CRISPR/Cas9 technology is used to disrupt five highly homologous gene paralogs through the targeting of exon 2 using a combination of four gRNAs, deleting 74 kb (103822963-103897826), resulting in the excision of Serpina1a and 1c. Null status was confirmed by transcriptome analysis. Western blot confirmed absence of the alpha1-antitrypsin protein in serum. (J:259615)