Cell-penetrating peptides-based strategies for the delivery of splice redirecting antisense oligonucleotides.

Journal article

Progress in our understanding of the molecular pathogenesis of human malignancies has provided therapeutic targets amenable to oligonucleotide (ON)-based strategies. Antisense ON-mediated splicing regulation in particular offers promising prospects since the majority of human genes undergo alternative splicing and since splicing defects have been found in many diseases. However, their implementation has been hampered so far by the poor bioavailability of nucleic acids-based drugs. Cell-penetrating peptides (CPPs) now appear as promising non-viral delivery vector for non-permeant biomolecules. We describe here new CPPs allowing the delivery of splice redirecting steric-block ON using either chemical conjugation or non-covalent complexation. We also describe a convenient and robust splice redirecting assay which allows the quantitative assessment of ON nuclear delivery.

Authors: Andaloussi, S; Said Hassane, F; Boisguerin, P; Sillard, R; Langel, U

• Journal: Methods in molecular biology (Clifton, N.J.)
• Volume: 764
• Pages: 75-89
• Publication date: 2011-01-01
• DOI: 10.1007/978-1-61779-188-8_5
• EISSN: 1940-6029
• ISSN: 1064-3745
• Language: English
• Keywords: Drug Delivery Systems; RNA, Messenger; Molecular Sequence Data; Humans; Hela Cells; Biological Assay; Cell Nucleus; Alternative Splicing; Reverse Transcriptase Polymerase Chain Reaction; Luciferases; Flow Cytometry; Oligonucleotides, Antisense; Macromolecular Substances; Amino Acid Sequence; Stearic Acids; Female; Genes, Reporter; Cell-Penetrating Peptides