Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein
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- Melissa Burton
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
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- Hiroyuki Nakai
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
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- Peter Colosi
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
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- Janet Cunningham
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
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- Rachel Mitchell
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
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- Linda Couto
- Avigen Inc., 1201 Harbor Bay Parkway, Alameda, CA 94502
抄録
<jats:p>We are interested in using recombinant adeno-associated viral vectors in the treatment of hemophilia A. Because of the size constraints of recombinant adeno-associated viral vectors, we delivered the heavy and light chains of the human factor 8 (hFVIII) cDNA independently by using two separate vectors. Recombinant AAV vectors were constructed that utilized the human elongation factor 1α promoter, a human growth factor polyadenylation signal, and the cDNA sequences encoding either the heavy or light chain of hFVIII. Portal vein injections of each vector alone, a combination of both vectors, or a hFIX control vector were performed in C57BL/6 mice. An ELISA specific for the light chain of hFVIII demonstrated very high levels (2–10 μg/ml) of protein expression in animals injected with the light chain vector alone or with both vectors. We utilized a chromogenic assay in combination with an antibody specific to hFVIII to determine the amount of biologically active hFVIII in mouse plasma. In animals injected with both the heavy and light chain vectors, greater than physiological levels (200–400 ng/ml) of biologically active hFVIII were produced. This suggests that coexpression of the heavy and light chains of hFVIII may be a feasible approach for treatment of hemophilia A.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 96 (22), 12725-12730, 1999-10-26
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1360855569564688128
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- NII論文ID
- 80010755178
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- ISSN
- 10916490
- 00278424
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- データソース種別
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