Wenjing Cao, Biao Dong, Franziska Horling, Jenni A Firrman, Johannes Lengler, Matthias Klugmann, Maurus de la Rosa, Wenman Wu, Qizhao Wang, Hongying Wei, Andrea R Moore, Sean A Roberts, Carmen J Booth, Werner Hoellriegl, Dong Li, Barbara Konkle, Carol Miao, Birgit M Reipert, Friedrich Scheiflinger, Hanspeter Rottensteiner, Weidong Xiao
One important limitation for achieving therapeutic expression of human factor VIII (FVIII) in hemophilia A gene therapy is inefficient secretion of the FVIII protein. Substitution of five amino acids in the A1 domain of human FVIII with the corresponding porcine FVIII residues generated a secretion-enhanced human FVIII variant termed B-domain-deleted (BDD)-FVIII-X5 that resulted in 8-fold higher FVIII activity levels in the supernatant of an in vitro cell-based assay system than seen with unmodified human BDD-FVIII...
December 11, 2020: Molecular Therapy. Methods & Clinical Development