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 90 kb ((103731876-103822024)) resulting in the excision of Serpina1b and 1d. Null status was confirmed by transcriptome analysis. Western blot confirmed absence of the alpha1-antitrypsin protein in serum. (J:259615)