Base Editing Reduces Misfolded Protein Accumulation and Toxicity in Alpha-1 Antitrypsin Deficient Patient iPSC-Hepatocytes

This study evaluates the efficiency and biological consequences of base editing of the single base "Z_ mutation in the SERIPNA1 gene responsible for causing misfolding of the alpha-1 antitrypsin protein that leads to the clinical disease "alpha-1 antitrypsin deficiency". Samples on which the editing is performed are patient-derived iPSCs from a single PiZZ patient. The iPSC line is named "PiZZ-1_. To evaluate possible off-target editing, 5 samples underwent whole genome sequencing. These samples include: 1) PiZZ-1 patient iPSCs at passage 34 ("ZZ p34_); 2) PiZZ-1 patient iPSCs at passage 42 ("ZZ p42_); 3) PiZZ-1 patient iPSCs that underwent nucleofection but not base editing at passage 34, and then were passaged until passage 42 ("ZZ nucleofected_); 4) PiZZ-1... (for more see dbGaP study page.)