Bioengineering coagulation factors for improved hemophilia treatments☆

The implementation of prophylaxis with regular factor VIII (FVIII) replacement for patients with hemophilia radically changed the clinical presentation of this condition, from a disease characterized by progressive disabling musculoskeletal complications, to one compatible with an active and virtually normal lifestyle. In Brazil, although most adults with severe hemophilia still suffer the impact of musculoskeletal complications in their quality of life,1 the recent implementation of universal prophylaxis will certainly change this situation for the next generation of patients. This scenario posits a challenge to government and healthcare providers, for whom guaranteeing a reliable and safe source of FVIII concentrate has become more than ever, a strategic issue. This is the context that underscores the importance of the study by Fantacini et al. in this issue of the Revista Brasileira de Hematologia e Hemoterapia, in which the authors used a combined strategy to improve recombinant FVIII production, based on ‘rational mutagenesis’, chemical chaperones, and human cell lines.2 Rational mutagenesis consists in the introduction of DNA variations (and hence, amino acid changes) aimed at improving the function of a recombinant protein, based on previous knowledge about protein structure and function. The power of rational mutagenesis was well-illustrated by the identification in 1988 of a residue in coagulation factor IX (FIX) whose change