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 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.
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Franziska
F
Zeyer
Department of Pharmacology and Experimental Therapy and ICePhA, University of Tübingen, Tübingen, Germany.
Benedikt
B
Mothes
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Clara
C
Will
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Melanie
M
Carevic
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Jennifer
J
Rottenberger
Department of Pharmacology and Experimental Therapy and ICePhA, University of Tübingen, Tübingen, Germany.
Bernd
B
Nürnberg
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Dominik
D
Hartl
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Rupert
R
Handgretinger
Department of Pharmacology and Experimental Therapy and ICePhA, University of Tübingen, Tübingen, Germany.
Sandra
S
Beer-Hammer
Department of Pediatrics I - Pediatric Infectiology and Immunology - Translational Genomics and Gene Therapy, University of Tübingen, Tübingen, Germany.
Michael S D
MS
Kormann
D000818:Animals; D001249:Asthma / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*
D012333:RNA, Messenger; D051193:Toll-Like Receptors