mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo.
Asthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several stud...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4839613?pdf=render |
| _version_ | 1828340269000425472 |
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| author | Franziska Zeyer Benedikt Mothes Clara Will Melanie Carevic Jennifer Rottenberger Bernd Nürnberg Dominik Hartl Rupert Handgretinger Sandra Beer-Hammer Michael S D Kormann |
| author_facet | Franziska Zeyer Benedikt Mothes Clara Will Melanie Carevic Jennifer Rottenberger Bernd Nürnberg Dominik Hartl Rupert Handgretinger Sandra Beer-Hammer Michael S D Kormann |
| author_sort | Franziska Zeyer |
| collection | DOAJ |
| description | Asthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several studies have suggested protective effects of Toll-like receptor (TLR) activation. We showed previously that modified mRNA provides a safe and efficient therapeutic tool for in vivo gene supplementation. Since current asthma drugs do not take patient specific immune and TLR backgrounds into consideration, treatment with tailored mRNA could be an attractive approach to account for the patient's individual asthma phenotype. Therefore, we investigated the effect of a preventative treatment with combinations of Tlr1, Tlr2 and Tlr6 mRNA in a House Dust Mite-induced mouse model of asthma. We used chemically modified mRNA which is-in contrast to conventional viral vectors-non-integrating and highly efficient in gene transfer. In our study, we found that treatment with either Tlr1/2 mRNA or Tlr2/6 mRNA, but not Tlr2 mRNA alone, resulted in better lung function as well as reduced airway inflammation in vivo. The present results point to a potentially protective effect of TLR heterodimers in asthma pathogenesis. |
| first_indexed | 2024-04-13T22:54:17Z |
| format | Article |
| id | doaj.art-beeaad1c81c6423880f268e6c4e20117 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T22:54:17Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-beeaad1c81c6423880f268e6c4e201172022-12-22T02:26:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015400110.1371/journal.pone.0154001mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo.Franziska ZeyerBenedikt MothesClara WillMelanie CarevicJennifer RottenbergerBernd NürnbergDominik HartlRupert HandgretingerSandra Beer-HammerMichael S D KormannAsthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several studies have suggested protective effects of Toll-like receptor (TLR) activation. We showed previously that modified mRNA provides a safe and efficient therapeutic tool for in vivo gene supplementation. Since current asthma drugs do not take patient specific immune and TLR backgrounds into consideration, treatment with tailored mRNA could be an attractive approach to account for the patient's individual asthma phenotype. Therefore, we investigated the effect of a preventative treatment with combinations of Tlr1, Tlr2 and Tlr6 mRNA in a House Dust Mite-induced mouse model of asthma. We used chemically modified mRNA which is-in contrast to conventional viral vectors-non-integrating and highly efficient in gene transfer. In our study, we found that treatment with either Tlr1/2 mRNA or Tlr2/6 mRNA, but not Tlr2 mRNA alone, resulted in better lung function as well as reduced airway inflammation in vivo. The present results point to a potentially protective effect of TLR heterodimers in asthma pathogenesis.http://europepmc.org/articles/PMC4839613?pdf=render |
| spellingShingle | Franziska Zeyer Benedikt Mothes Clara Will Melanie Carevic Jennifer Rottenberger Bernd Nürnberg Dominik Hartl Rupert Handgretinger Sandra Beer-Hammer Michael S D Kormann mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. PLoS ONE |
| title | mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. |
| title_full | mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. |
| title_fullStr | mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. |
| title_full_unstemmed | mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. |
| title_short | mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo. |
| title_sort | mrna mediated gene supplementation of toll like receptors as treatment strategy for asthma in vivo |
| url | http://europepmc.org/articles/PMC4839613?pdf=render |
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