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Overview of Alternative Oligonucleotide Chemistries for Exon Skipping

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Exon Skipping

Part of the book series: Methods in Molecular Biology ((MIMB,volume 867))

Abstract

The chemistry of the oligonucleotide backbone is crucial to obtaining high activity in vivo in exon skipping applications. Apart from the ability to bind strongly and sequence-specifically to pre-mRNA targets, the type of backbone also influences cell delivery, in vivo pharmacology, bio-distribution, toxicology, and ultimately the therapeutic use in humans. Reviewed here are classes of oligonucleotide commonly used for exon skipping applications, namely negatively charged backbones typified by RNA analogues having 2′-O-substitution and a phosphorothioate linkage and charge-neutral backbones such as PNA and PMO. Also discussed are peptide conjugates of PNA and PMO that enhance cellular and in vivo delivery and their potential for drug development. Finally, the prospects for development of other analogue types in exon skipping applications are outlined.

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Acknowledgements

Work in the Gait laboratory is supported by the Medical Research Council (Unit programme U105178803). We thank Matthew Wood and Haifang Yin (University of Oxford) for a fruitful and stimulating collaboration in exon skipping applications of ONs and for comments on this manuscript.

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  1. Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK

    Amer F. Saleh, Andrey A. Arzumanov & Michael J. Gait

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  1. Amer F. Saleh
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  2. Andrey A. Arzumanov
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  3. Michael J. Gait
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Correspondence to Michael J. Gait .

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  1. Dept. Human & Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, Leiden, 2333 ZC, Netherlands

    Annemieke Aartsma-Rus

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Saleh, A.F., Arzumanov, A.A., Gait, M.J. (2012). Overview of Alternative Oligonucleotide Chemistries for Exon Skipping. In: Aartsma-Rus, A. (eds) Exon Skipping. Methods in Molecular Biology, vol 867. Humana Press. https://doi.org/10.1007/978-1-61779-767-5_23

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  • DOI: https://doi.org/10.1007/978-1-61779-767-5_23

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