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  • Original Article
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Correction of dystrophia myotonica type 1 pre-mRNA transcripts by artificial trans-splicing

Gene Therapy volume 16, pages 211–217 (2009)Cite this article

Abstract

Dystrophia myotonica type 1 (DM1), the most common muscular dystrophy in adults, results from expansion of a CTG repeat in the 3′-untranslated region of the dystrophia myotonica protein kinase gene (DMPK). Correction of the mutant DMPK transcript is a potential therapeutic strategy in DM1. We investigated the efficacy of artificial trans-splicing molecules (ATMs) to target and correct DMPK transcripts. ATMs designed to target intron 14 of DMPK pre-mRNA transcripts were tested for their ability to trans-splice the transcripts of a DMPK mini-gene construct and the endogenous DMPK transcripts of human myosarcoma cells (CCL-136). On agarose gel electrophoresis analysis, six of eight ATMs showed trans-splicing efficacy when applied to DMPK mini-gene construct transcripts, of which three were able to trans-splice endogenous DMPK pre-mRNA transcripts in myosarcoma cells, with trans-splicing efficiency ranging from 1.81 to 7.41%. These findings confirm that artificial trans-splicing can repair DMPK pre-mRNA and provide proof-of-principle evidence for this approach as potential therapeutic strategy for DM1.

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Acknowledgements

HY Chen was supported in part by a scholarship from the Singapore Millennium Foundation to conduct this study. This study was supported by the following grants from the National Medical Research Council of Singapore—NMRC/0607/2001 and NMRC/1098/2006.

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Author notes

  1. H Y Chen, P Kathirvel & W C Yee

    Present address: 3Current address: Department of Clinical Research, Singapore General Hospital, Singapore.,

  2. H Y Chen and P Kathirvel: These two authors contributed equally to this work.

Authors and Affiliations

  1. Research Division, Neuromuscular Research Laboratory, National Neuroscience Institute, Singapore

    H Y Chen, P Kathirvel & W C Yee

  2. Department of Paediatrics, Human Molecular Genetics Laboratory, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    P S Lai

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  1. H Y Chen
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Correspondence to W C Yee.

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Chen, H., Kathirvel, P., Yee, W. et al. Correction of dystrophia myotonica type 1 pre-mRNA transcripts by artificial trans-splicing. Gene Ther 16, 211–217 (2009). https://doi.org/10.1038/gt.2008.150

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