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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224270/ https://www.ncbi.nlm.nih.gov/pubmed/25383359 http://dx.doi.org/10.1038/mtm.2013.8 |
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author | Liu, Xianglan Magee, Daniel Wang, Chuansong McMurphy, Travis Slater, Andrew During, Matthew Cao, Lei |
author_facet | Liu, Xianglan Magee, Daniel Wang, Chuansong McMurphy, Travis Slater, Andrew During, Matthew Cao, Lei |
author_sort | Liu, Xianglan |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4224270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42242702014-11-07 Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype Liu, Xianglan Magee, Daniel Wang, Chuansong McMurphy, Travis Slater, Andrew During, Matthew Cao, Lei Mol Ther Methods Clin Dev Article 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. Nature Publishing Group 2014-02-05 /pmc/articles/PMC4224270/ /pubmed/25383359 http://dx.doi.org/10.1038/mtm.2013.8 Text en Copyright © 2014 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Article Liu, Xianglan Magee, Daniel Wang, Chuansong McMurphy, Travis Slater, Andrew During, Matthew Cao, Lei Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224270/ https://www.ncbi.nlm.nih.gov/pubmed/25383359 http://dx.doi.org/10.1038/mtm.2013.8 |
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