Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype
Adipose tissue plays an essential role in metabolic homeostasis and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissue in vivo have yet to be established. Here, we assessed the transduction efficiency to fat depots by a family...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116300730 |
| _version_ | 1819143952048062464 |
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| author | Xianglan Liu Daniel Magee Chuansong Wang Travis McMurphy Andrew Slater Matthew During Lei Cao |
| author_facet | Xianglan Liu Daniel Magee Chuansong Wang Travis McMurphy Andrew Slater Matthew During Lei Cao |
| author_sort | Xianglan Liu |
| collection | DOAJ |
| description | Adipose tissue plays an essential role in metabolic homeostasis and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissue in vivo have yet to be established. Here, we assessed the transduction efficiency to fat depots by a family of novel engineered hybrid capsid serotypes (Rec1∼4) recombinant adeno-associated viral (AAV) vectors in comparison with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread transduction in both brown fat and white fat with the highest efficiency among the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to deliver Cre recombinase to adipose tissues of insulin receptor floxed animals. Insulin receptor knockdown led to decreased fat pad mass and morphological and molecular changes in the targeted depot. These novel hybrid AAV vectors can serve as powerful tools to genetically manipulate adipose tissue and provide valuable vehicles to gene therapy targeting adipose tissue. |
| first_indexed | 2024-12-22T12:34:24Z |
| format | Article |
| id | doaj.art-3d8d90e1c95e45e3b9a160f21ab2b86b |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-22T12:34:24Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-3d8d90e1c95e45e3b9a160f21ab2b86b2022-12-21T18:25:35ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012014-01-011C10.1038/mtm.2013.8Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotypeXianglan Liu0Daniel Magee1Chuansong Wang2Travis McMurphy3Andrew Slater4Matthew During5Lei Cao6Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USAAdipose tissue plays an essential role in metabolic homeostasis and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissue in vivo have yet to be established. Here, we assessed the transduction efficiency to fat depots by a family of novel engineered hybrid capsid serotypes (Rec1∼4) recombinant adeno-associated viral (AAV) vectors in comparison with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread transduction in both brown fat and white fat with the highest efficiency among the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to deliver Cre recombinase to adipose tissues of insulin receptor floxed animals. Insulin receptor knockdown led to decreased fat pad mass and morphological and molecular changes in the targeted depot. These novel hybrid AAV vectors can serve as powerful tools to genetically manipulate adipose tissue and provide valuable vehicles to gene therapy targeting adipose tissue.http://www.sciencedirect.com/science/article/pii/S2329050116300730 |
| spellingShingle | Xianglan Liu Daniel Magee Chuansong Wang Travis McMurphy Andrew Slater Matthew During Lei Cao Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype Molecular Therapy: Methods & Clinical Development |
| title | Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
| title_full | Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
| title_fullStr | Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
| title_full_unstemmed | Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
| title_short | Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
| title_sort | adipose tissue insulin receptor knockdown via a new primate derived hybrid recombinant aav serotype |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116300730 |
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