Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy
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-do...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050118301311 |
| _version_ | 1818608405723480064 |
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| author | Benjamin J. Samelson-Jones Valder R. Arruda |
| author_facet | Benjamin J. Samelson-Jones Valder R. Arruda |
| author_sort | Benjamin J. Samelson-Jones |
| collection | DOAJ |
| description | 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. Keywords: Hemophilia A, hemophilia B, gene therapy, bioengineering, factor VIII, factor IX, factor IX Padua, B-domain delete factor VIII, immunogenicity, protein engineering |
| first_indexed | 2024-12-16T14:42:08Z |
| format | Article |
| id | doaj.art-332b5c1c4a394b8f91a27e35a4490dd4 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-16T14:42:08Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-332b5c1c4a394b8f91a27e35a4490dd42022-12-21T22:27:53ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012019-03-0112184201Protein-Engineered Coagulation Factors for Hemophilia Gene TherapyBenjamin J. Samelson-Jones0Valder R. Arruda1The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Philadelphia, PA, USAThe Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Philadelphia, PA, USA; Corresponding author: Valder R. Arruda, MD, PhD, The Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5056 Colket Translational Research Center, Philadelphia, PA 19104, USA.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. Keywords: Hemophilia A, hemophilia B, gene therapy, bioengineering, factor VIII, factor IX, factor IX Padua, B-domain delete factor VIII, immunogenicity, protein engineeringhttp://www.sciencedirect.com/science/article/pii/S2329050118301311 |
| spellingShingle | Benjamin J. Samelson-Jones Valder R. Arruda Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy Molecular Therapy: Methods & Clinical Development |
| title | Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy |
| title_full | Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy |
| title_fullStr | Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy |
| title_full_unstemmed | Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy |
| title_short | Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy |
| title_sort | protein engineered coagulation factors for hemophilia gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2329050118301311 |
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