title: Cell-penetrating peptides-based strategies for the delivery of splice redirecting antisense oligonucleotides.
abstract: 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: Department of Neurochemistry, Stockholm University, Stockholm, Sweden. samir.elandaloussi@dpag.ox.ac.uk
authors: Samir
authors: S
authors: El Andaloussi
authors: Fatouma
authors: F
authors: Said Hassane
authors: Prisca
authors: P
authors: Boisguerin
authors: Rannar
authors: R
authors: Sillard
authors: Ulo
authors: U
authors: Langel
authors: Bernard
authors: B
authors: Lebleu
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001681:Biological Assay; D002467:Cell Nucleus / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000032:analysis; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013229:Stearic Acids / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013229:Stearic Acids; C031183:stearic acid; D008156:Luciferases