Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy
Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deli...
| Autores principales: | , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | inglés |
| Publicado: |
2018
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| Materias: | |
| Acceso en línea: | http://eprints.uanl.mx/18918/1/genetherapy-2018-.pdf |
| _version_ | 1824415380365377536 |
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| author | Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. |
| author_facet | Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. |
| author_sort | Chen, Shuyuan |
| collection | Repositorio Institucional |
| description | Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a
potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a
novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to
engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol
using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main
findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh,
achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss
obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food
intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in
SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogeni |
| format | Article |
| id | eprints-18918 |
| institution | UANL |
| language | English |
| publishDate | 2018 |
| record_format | eprints |
| spelling | eprints-189182020-05-21T19:47:29Z http://eprints.uanl.mx/18918/ Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. R Medicina en General Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogeni 2018-08 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/18918/1/genetherapy-2018-.pdf http://eprints.uanl.mx/18918/1.haspreviewThumbnailVersion/genetherapy-2018-.pdf Chen, Shuyuan y Bastarrachea, Raúl A. y Shen, Jin Song y Laviada Nagel, Antonio y Rodríguez Ayala, Ernesto y Nava González, Edna Judith y Huang, Pintong y DeFronzo, Ralph A. y Kent, Jack W. y Grayburn, Paul A. (2018) Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. Gene Therapy, 25 (7). pp. 497-509. ISSN 0969-7128 http://doi.org/10.1038/s41434-018-0036-5 doi:10.1038/s41434-018-0036-5 |
| spellingShingle | R Medicina en General Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| title_full | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| title_fullStr | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| title_full_unstemmed | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| title_short | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy |
| title_sort | ectopic bat mucp 1 overexpression in skm by delivering a bmp7 prdm16 pgc 1a gene cocktail or single prmd16 using non viral utmd gene therapy |
| topic | R Medicina en General |
| url | http://eprints.uanl.mx/18918/1/genetherapy-2018-.pdf |
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