Hemophilia gene therapy comes of age
Open accessAbstract
Concurrent with the development of recombinant factor replacement products, the characterization of the F9 and F8 genes over 3 decades ago allowed for the development of recombinant factor products and made the hemophilias a target disease for gene transfer. The progress of hemophilia gene therapy has been announced in 3 American Society of Hematology scientific plenary sessions, including the first “cure” in a large animal model of hemophilia B in 1998, first in human sustained vector-derived factor IX activity in 2011, and our clinical trial results reporting sustained vector-derived factor IX activity well into the mild or normal range in 2016. This progression to clinically meaningful success combined with numerous ongoing recombinant adeno-associated virus (rAAV)–mediated hemophilia gene transfer clinical trials suggest that the goal of gene therapy to alter the paradigm of hemophilia care may soon be realized. Although several novel therapeutics have recently emerged for hemophilia, gene therapy is unique in its potential for a one-time disease-altering, or even curative, treatment. This review will focus on the prior progress and current clinical trial investigation of rAAV-mediated gene transfer for hemophilia A and B.
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Both FVIII-SQ and FIX-R338L demonstrate variable activity measurements in OSA versus chromogenic assay that are reproducible across trials.
“both transgene products, FVIII-SQ and FIX-R338L, demonstrate variable activity measurements in OSA versus chromogenic assay (CSA) determinants of factor activity that are reproducible across trials.144,145,149,152”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [144]
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Cites
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BackgroundCpG-depleted adeno-associated virus vectors evade immune detection
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Current clinical applications of in vivo gene therapy with AAVs
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- Authors
- George, L. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- George, Lindsey A.
- ORCID
- George, Lindsey A.
- Venue
- Hematology
- Publisher
- American Society of Hematology
- Published
- 2017-12-08
- Volume
- 2017
- Issue
- 1
- Pages
- 587-594
- ISSN
- 1520-4383 (ISSN-L)
- 1520-4391
- PMC
- PMC6142599
- OpenAlex
- W2781901028
- Cited by
- 58
- References
- 10
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 14 · 2019: 11 · 2018: 11
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hematology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007150)
- Topics
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- hemophilia A, hemophilia B, recombinant adeno-associated virus vectors, factor IX, factor VIII, curative treatment
- MeSH terms
- Dependovirus, Animals, Factor IX, Factor VIII, Hemophilia A, Humans, Transduction, Genetic, Genetic Therapy
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