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Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , |
| In: | Blood, 108, 2006, 1, S. 107-115 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
|
| Schlagwörter: |
| author_facet |
Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. |
|---|---|
| author |
Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. |
| spellingShingle |
Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. Blood Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs Cell Biology Hematology Immunology Biochemistry |
| author_sort |
jiang, haiyan |
| spelling |
Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-12-5115 <jats:p>Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy. Restoring 1% to 5% of normal blood FVIII activity prevents spontaneous bleeding, making the disease an attractive gene therapy target. Previously, we have demonstrated short-term activity of a liver-specific AAV2 vector expressing canine B-domain-deleted FVIII (cFVIII) in a hemophilia canine model. Here, we report the long-term efficacy and safety of AAV-cFVIII vectors of serotypes 2, 5, 6, and 8 in both hemophilia A mice and dogs. AAV6-cFVIII and AAV8-cFVIII restored physiologic levels of plasma FVIII activity in hemophilia A mice. The improved efficacy is attributed to more efficient gene transfer in liver compared with AAV2 and AAV5. However, supraphysiologic cFVIII levels correlated with the formation of cFVIII-neutralizing antibodies in these mice. Of importance, hemophilia A dogs that received AAV2-cFVIII, AAV6-cFVIII, and AAV8-cFVIII have persistently expressed therapeutic levels of FVIII, without antibody formation or other toxicities, for more than 3 years. However, liver transduction efficiencies are similar between AAV2, AAV6, and AAV8 serotypes in hemophilia A dogs, in contrast to mice. In summary, this is the first report demonstrating multiyear therapeutic efficacy and safety of multiple AAV-cFVIII vectors in hemophilia A dogs and provides the basis for human clinical studies. (Blood. 2006;108:107-115)</jats:p> Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs Blood |
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| title |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_unstemmed |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_full |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_fullStr |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_full_unstemmed |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_short |
Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_sort |
multiyear therapeutic benefit of aav serotypes 2, 6, and 8 delivering factor viii to hemophilia a mice and dogs |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2005-12-5115 |
| publishDate |
2006 |
| physical |
107-115 |
| description |
<jats:p>Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy. Restoring 1% to 5% of normal blood FVIII activity prevents spontaneous bleeding, making the disease an attractive gene therapy target. Previously, we have demonstrated short-term activity of a liver-specific AAV2 vector expressing canine B-domain-deleted FVIII (cFVIII) in a hemophilia canine model. Here, we report the long-term efficacy and safety of AAV-cFVIII vectors of serotypes 2, 5, 6, and 8 in both hemophilia A mice and dogs. AAV6-cFVIII and AAV8-cFVIII restored physiologic levels of plasma FVIII activity in hemophilia A mice. The improved efficacy is attributed to more efficient gene transfer in liver compared with AAV2 and AAV5. However, supraphysiologic cFVIII levels correlated with the formation of cFVIII-neutralizing antibodies in these mice. Of importance, hemophilia A dogs that received AAV2-cFVIII, AAV6-cFVIII, and AAV8-cFVIII have persistently expressed therapeutic levels of FVIII, without antibody formation or other toxicities, for more than 3 years. However, liver transduction efficiencies are similar between AAV2, AAV6, and AAV8 serotypes in hemophilia A dogs, in contrast to mice. In summary, this is the first report demonstrating multiyear therapeutic efficacy and safety of multiple AAV-cFVIII vectors in hemophilia A dogs and provides the basis for human clinical studies. (Blood. 2006;108:107-115)</jats:p> |
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| author | Jiang, Haiyan, Lillicrap, David, Patarroyo-White, Susannah, Liu, Tongyao, Qian, Xiaobing, Scallan, Ciaran D., Powell, Sandra, Keller, Tracey, McMurray, Morag, Labelle, Andrea, Nagy, Dea, Vargas, Joseph A., Zhou, Shangzhen, Couto, Linda B., Pierce, Glenn F. |
| author_facet | Jiang, Haiyan, Lillicrap, David, Patarroyo-White, Susannah, Liu, Tongyao, Qian, Xiaobing, Scallan, Ciaran D., Powell, Sandra, Keller, Tracey, McMurray, Morag, Labelle, Andrea, Nagy, Dea, Vargas, Joseph A., Zhou, Shangzhen, Couto, Linda B., Pierce, Glenn F., Jiang, Haiyan, Lillicrap, David, Patarroyo-White, Susannah, Liu, Tongyao, Qian, Xiaobing, Scallan, Ciaran D., Powell, Sandra, Keller, Tracey, McMurray, Morag, Labelle, Andrea, Nagy, Dea, Vargas, Joseph A., Zhou, Shangzhen, Couto, Linda B., Pierce, Glenn F. |
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| description | <jats:p>Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy. Restoring 1% to 5% of normal blood FVIII activity prevents spontaneous bleeding, making the disease an attractive gene therapy target. Previously, we have demonstrated short-term activity of a liver-specific AAV2 vector expressing canine B-domain-deleted FVIII (cFVIII) in a hemophilia canine model. Here, we report the long-term efficacy and safety of AAV-cFVIII vectors of serotypes 2, 5, 6, and 8 in both hemophilia A mice and dogs. AAV6-cFVIII and AAV8-cFVIII restored physiologic levels of plasma FVIII activity in hemophilia A mice. The improved efficacy is attributed to more efficient gene transfer in liver compared with AAV2 and AAV5. However, supraphysiologic cFVIII levels correlated with the formation of cFVIII-neutralizing antibodies in these mice. Of importance, hemophilia A dogs that received AAV2-cFVIII, AAV6-cFVIII, and AAV8-cFVIII have persistently expressed therapeutic levels of FVIII, without antibody formation or other toxicities, for more than 3 years. However, liver transduction efficiencies are similar between AAV2, AAV6, and AAV8 serotypes in hemophilia A dogs, in contrast to mice. In summary, this is the first report demonstrating multiyear therapeutic efficacy and safety of multiple AAV-cFVIII vectors in hemophilia A dogs and provides the basis for human clinical studies. (Blood. 2006;108:107-115)</jats:p> |
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| spelling | Jiang, Haiyan Lillicrap, David Patarroyo-White, Susannah Liu, Tongyao Qian, Xiaobing Scallan, Ciaran D. Powell, Sandra Keller, Tracey McMurray, Morag Labelle, Andrea Nagy, Dea Vargas, Joseph A. Zhou, Shangzhen Couto, Linda B. Pierce, Glenn F. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-12-5115 <jats:p>Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy. Restoring 1% to 5% of normal blood FVIII activity prevents spontaneous bleeding, making the disease an attractive gene therapy target. Previously, we have demonstrated short-term activity of a liver-specific AAV2 vector expressing canine B-domain-deleted FVIII (cFVIII) in a hemophilia canine model. Here, we report the long-term efficacy and safety of AAV-cFVIII vectors of serotypes 2, 5, 6, and 8 in both hemophilia A mice and dogs. AAV6-cFVIII and AAV8-cFVIII restored physiologic levels of plasma FVIII activity in hemophilia A mice. The improved efficacy is attributed to more efficient gene transfer in liver compared with AAV2 and AAV5. However, supraphysiologic cFVIII levels correlated with the formation of cFVIII-neutralizing antibodies in these mice. Of importance, hemophilia A dogs that received AAV2-cFVIII, AAV6-cFVIII, and AAV8-cFVIII have persistently expressed therapeutic levels of FVIII, without antibody formation or other toxicities, for more than 3 years. However, liver transduction efficiencies are similar between AAV2, AAV6, and AAV8 serotypes in hemophilia A dogs, in contrast to mice. In summary, this is the first report demonstrating multiyear therapeutic efficacy and safety of multiple AAV-cFVIII vectors in hemophilia A dogs and provides the basis for human clinical studies. (Blood. 2006;108:107-115)</jats:p> Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs Blood |
| spellingShingle | Jiang, Haiyan, Lillicrap, David, Patarroyo-White, Susannah, Liu, Tongyao, Qian, Xiaobing, Scallan, Ciaran D., Powell, Sandra, Keller, Tracey, McMurray, Morag, Labelle, Andrea, Nagy, Dea, Vargas, Joseph A., Zhou, Shangzhen, Couto, Linda B., Pierce, Glenn F., Blood, Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_full | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_fullStr | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_full_unstemmed | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_short | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| title_sort | multiyear therapeutic benefit of aav serotypes 2, 6, and 8 delivering factor viii to hemophilia a mice and dogs |
| title_unstemmed | Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2005-12-5115 |