Summary
Several strategies based on synthetic oligonucleotides (ON) have been proposed to control gene expression. As for most biomolecules, however, delivery has remained a major roadblock for in vivo applications. Conjugation of steric-block neutral DNA mimics such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligonucleotides (PMO) to cell penetrating peptides (CPP) has recently been proposed as a new delivery strategy. It is particularly suitable to interfere sequence-specifically with pre-mRNA splicing thus offering various applications in fundamental research and in therapeutics. The chemical synthesis of these CPP conjugates as well as methodologies to monitor their cellular uptake and their efficiency in a reliable and easy to implement assay of splicing correction will be described.
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Acknowledgements
We thank R. Kole (University North Carolina) for providing the pLuc705 cell line. Studies funded by EC grant QLK3-CT-2002-01989 and CEFIPRA grant 3205. S. Abes had a pre-doctoral fellowship from the Ligue Regionale contre le Cancer and R. Abes had a Region Languedoc-Roussillon training fellowship.
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Abes, S. et al. (2009). Peptide-Based Delivery of Steric-Block PNA Oligonucleotides. In: Belting, M. (eds) Macromolecular Drug Delivery. Methods in Molecular Biology, vol 480. Humana Press. https://doi.org/10.1007/978-1-59745-429-2_6
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DOI: https://doi.org/10.1007/978-1-59745-429-2_6
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