Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors.
In recent years, the increasing prevalence of obesity and obesity-related co-morbidities fostered intensive research in the field of adipose tissue biology. To further unravel molecular mechanisms of adipose tissue function, genetic tools enabling functional studies in vitro and in vivo are essentia...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4281237?pdf=render |
| _version_ | 1811280375534583808 |
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| author | Silke Uhrig-Schmidt Matthias Geiger Gerd Luippold Gerald Birk Detlev Mennerich Heike Neubauer Dirk Grimm Christian Wolfrum Sebastian Kreuz |
| author_facet | Silke Uhrig-Schmidt Matthias Geiger Gerd Luippold Gerald Birk Detlev Mennerich Heike Neubauer Dirk Grimm Christian Wolfrum Sebastian Kreuz |
| author_sort | Silke Uhrig-Schmidt |
| collection | DOAJ |
| description | In recent years, the increasing prevalence of obesity and obesity-related co-morbidities fostered intensive research in the field of adipose tissue biology. To further unravel molecular mechanisms of adipose tissue function, genetic tools enabling functional studies in vitro and in vivo are essential. While the use of transgenic animals is well established, attempts using viral and non-viral vectors to genetically modify adipocytes in vivo are rare. Therefore, we here characterized recombinant Adeno-associated virus (rAAV) vectors regarding their potency as gene transfer vehicles for adipose tissue. Our results demonstrate that a single dose of systemically applied rAAV8-CMV-eGFP can give rise to remarkable transgene expression in murine adipose tissues. Upon transcriptional targeting of the rAAV8 vector to adipocytes using a 2.2 kb fragment of the murine adiponectin (mAP2.2) promoter, eGFP expression was significantly decreased in off-target tissues while efficient transduction was maintained in subcutaneous and visceral fat depots. Moreover, rAAV8-mAP2.2-mediated expression of perilipin A - a lipid-droplet-associated protein - resulted in significant changes in metabolic parameters only three weeks post vector administration. Taken together, our findings indicate that rAAV vector technology is applicable as a flexible tool to genetically modify adipocytes for functional proof-of-concept studies and the assessment of putative therapeutic targets in vivo. |
| first_indexed | 2024-04-13T01:13:34Z |
| format | Article |
| id | doaj.art-a3b930ad47f2415bbd516a3b9c3a7200 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T01:13:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a3b930ad47f2415bbd516a3b9c3a72002022-12-22T03:09:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11628810.1371/journal.pone.0116288Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors.Silke Uhrig-SchmidtMatthias GeigerGerd LuippoldGerald BirkDetlev MennerichHeike NeubauerDirk GrimmChristian WolfrumSebastian KreuzIn recent years, the increasing prevalence of obesity and obesity-related co-morbidities fostered intensive research in the field of adipose tissue biology. To further unravel molecular mechanisms of adipose tissue function, genetic tools enabling functional studies in vitro and in vivo are essential. While the use of transgenic animals is well established, attempts using viral and non-viral vectors to genetically modify adipocytes in vivo are rare. Therefore, we here characterized recombinant Adeno-associated virus (rAAV) vectors regarding their potency as gene transfer vehicles for adipose tissue. Our results demonstrate that a single dose of systemically applied rAAV8-CMV-eGFP can give rise to remarkable transgene expression in murine adipose tissues. Upon transcriptional targeting of the rAAV8 vector to adipocytes using a 2.2 kb fragment of the murine adiponectin (mAP2.2) promoter, eGFP expression was significantly decreased in off-target tissues while efficient transduction was maintained in subcutaneous and visceral fat depots. Moreover, rAAV8-mAP2.2-mediated expression of perilipin A - a lipid-droplet-associated protein - resulted in significant changes in metabolic parameters only three weeks post vector administration. Taken together, our findings indicate that rAAV vector technology is applicable as a flexible tool to genetically modify adipocytes for functional proof-of-concept studies and the assessment of putative therapeutic targets in vivo.http://europepmc.org/articles/PMC4281237?pdf=render |
| spellingShingle | Silke Uhrig-Schmidt Matthias Geiger Gerd Luippold Gerald Birk Detlev Mennerich Heike Neubauer Dirk Grimm Christian Wolfrum Sebastian Kreuz Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. PLoS ONE |
| title | Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. |
| title_full | Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. |
| title_fullStr | Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. |
| title_full_unstemmed | Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. |
| title_short | Gene delivery to adipose tissue using transcriptionally targeted rAAV8 vectors. |
| title_sort | gene delivery to adipose tissue using transcriptionally targeted raav8 vectors |
| url | http://europepmc.org/articles/PMC4281237?pdf=render |
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