Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.
We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3610755?pdf=render |
| _version_ | 1811212372516274176 |
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| author | Masaru Shimada Shinya Abe Toru Takahashi Kazumasa Shiozaki Mitsue Okuda Hiroaki Mizukami Dennis M Klinman Keiya Ozawa Kenji Okuda |
| author_facet | Masaru Shimada Shinya Abe Toru Takahashi Kazumasa Shiozaki Mitsue Okuda Hiroaki Mizukami Dennis M Klinman Keiya Ozawa Kenji Okuda |
| author_sort | Masaru Shimada |
| collection | DOAJ |
| description | We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0×10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-Aß Ab levels up to 0.3 mg/ml. Anti-Aß Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on Aß levels in vivo was examined. A significant decrease in Aß levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-Aß Ab for the prevention and treatment of Alzheimer's disease. |
| first_indexed | 2024-04-12T05:28:24Z |
| format | Article |
| id | doaj.art-bb5584f2f78548e1b4006193324b91db |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:28:24Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bb5584f2f78548e1b4006193324b91db2022-12-22T03:46:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5760610.1371/journal.pone.0057606Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.Masaru ShimadaShinya AbeToru TakahashiKazumasa ShiozakiMitsue OkudaHiroaki MizukamiDennis M KlinmanKeiya OzawaKenji OkudaWe previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0×10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-Aß Ab levels up to 0.3 mg/ml. Anti-Aß Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on Aß levels in vivo was examined. A significant decrease in Aß levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-Aß Ab for the prevention and treatment of Alzheimer's disease.http://europepmc.org/articles/PMC3610755?pdf=render |
| spellingShingle | Masaru Shimada Shinya Abe Toru Takahashi Kazumasa Shiozaki Mitsue Okuda Hiroaki Mizukami Dennis M Klinman Keiya Ozawa Kenji Okuda Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. PLoS ONE |
| title | Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. |
| title_full | Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. |
| title_fullStr | Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. |
| title_full_unstemmed | Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. |
| title_short | Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein. |
| title_sort | prophylaxis and treatment of alzheimer s disease by delivery of an adeno associated virus encoding a monoclonal antibody targeting the amyloid beta protein |
| url | http://europepmc.org/articles/PMC3610755?pdf=render |
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