Work

Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy

Year: 2018

Type: review

Abstract: Hemophilia A (HA) and hemophilia B (HB) are X-linked bleeding disorders due to inheritable deficiencies in either coagulation factor VIII (FVIII) or factor IX (FIX), respectively. Recently, gene therapy clinical trials with adeno-associated virus (AAV) vectors and protein-engineered transgenes, B-domain deleted (BDD) FVIII and FIX-Padua, have reported near-phenotypic cures in subjects with HA and HB, respectively. Here, we review the biology and the clinical development of FVIII-BDD and FIX-Padua as transgenes. We also examine alternative bioengineering strategies for FVIII and FIX, as well as the immunological challenges of these approaches. Other engineered proteins and their potential use in gene therapy for hemophilia with inhibitors are also discussed. Continued advancement of gene therapy for HA and HB using protein-engineered transgenes has the potential to alleviate the substantial medical and psychosocial burdens of the disease.

Source: Molecular Therapy — Methods & Clinical Development

DOI: 10.1016/j.omtm.2018.12.007

Authors: Benjamin J. Samelson-Jones, Valder R. Arruda

Institutions: Children's Hospital of Philadelphia, University of Pennsylvania

Language: English

Topic: Hemophilia Treatment and Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,900