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Recombinant factor IX secreted by transduced human keratinocytes is biologically active
A J Gerrard1, D E Austen, G G Brownlee
1Chemical Pathology Unit, Sir William Dunn School of Pathology, University of Oxford.
British Journal of Haematology
|December 1, 1996
Summary
Gene therapy for haemophilia B using human keratinocytes shows promising results. Recombinant factor IX secreted by these cells is now found to be nearly fully biologically active, suggesting potential for effective treatment.
Area of Science:
- Biotechnology
- Gene Therapy
- Dermatology
Background:
- Haemophilia B is a genetic bleeding disorder caused by a deficiency in factor IX.
- Gene therapy aims to treat haemophilia B by enabling target cells to produce functional factor IX.
- Human keratinocytes are being investigated as potential cellular vehicles for factor IX delivery.
Purpose of the Study:
- To evaluate the biological activity of recombinant factor IX secreted by gene-modified human keratinocytes.
- To assess the suitability of keratinocytes for developing a gene therapy approach for haemophilia B.
- To address previous concerns regarding the reduced activity of secreted factor IX.
Main Methods:
- Transduction of human keratinocytes with a vector encoding factor IX.
- Culturing of engineered keratinocytes to assess factor IX secretion.
- Utilizing an alternative assay to measure the biological activity of the secreted recombinant factor IX.
Main Results:
- Previous studies reported recombinant factor IX with only 40% biological activity.
- The current study, using a different assay, demonstrates that secreted factor IX is almost fully biologically active.
- This finding suggests improved functionality of factor IX produced by keratinocytes.
Conclusions:
- Human keratinocytes are a viable cell type for gene therapy of haemophilia B.
- The previously observed low activity of secreted factor IX may have been an artifact of the assay used.
- Engineered keratinocyte grafts secreting fully active factor IX represent a promising strategy for haemophilia B treatment.