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A Drosophila High-throughput Drug Screening Platform Identifies Inhibitors Of Misregulated Alternative Splicing Events In Myotonic Dystrophy | 17134
ISSN: 2155-952X

Journal of Biotechnology & Biomaterials
Open Access

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A Drosophila high-throughput drug screening platform identifies inhibitors of misregulated alternative splicing events in myotonic dystrophy

5th World Congress on Biotechnology

Ruben Artero, Irma Garcia, Jordi Colonques, Raquel Garijo, M Carmen Alvarez, Jose Ruben Tormo, Manuel Perez Alonso and Arturo Lopez Castel

ScientificTracks Abstracts: J Biotechnol Biomater

DOI: 10.4172/2155-952X.S1.027

Abstract
An automatedin vivo screening platform for the identification of molecules able to modulate alternative splicing events linked to human disease is introduced. The screening assay is based on the generation of transgenic flies that express a spliceosensor construct, this is, a minigene whose alternative splicing is coupled to the production of the luciferase reporter. For the Drosophila -based assay we took advantage of the fact that flies were able to closely mirror missplicing events associated to myotonic dystrophy type 1 (DM1), which is the first described human spliceopathy. The design of the high-throughput screening pilot study also implemented recent advances in fly assay miniaturization and automation, allowing a top screening speed of 1,000 compounds per week. Together, more that 15,000 small molecules, which constitutes one of the largest in vivo pharmacological screening to date were screened and identified more than 30 primary hits, several showing promising anti-DM1 properties according to their putative mechanisms of action and effect on molecular hallmarks of the disease. The Drosophila -based tools here described are valuable and flexible resources for innovative drug discovery on human pathologies originating from alternative splicing misregulation.
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