title: Identification of peptides for tissue-specific delivery.
abstract: Antisense-mediated exon skipping has shown to be a promising therapeutic approach and is in clinical trials for Duchenne muscular dystrophy. However, after systemic treatment the majority of the injected antisense oligonucleotides (AONs) will not end up in the intended tissue. This mistargeting of AONs might have detrimental effects, especially with long-term treatment and continuous accumulation of AONs. Further, even when no detrimental effects occur, mistargeted AONs are lost for exon skipping in the intended tissue. One way to reduce the amount of mistargeted AONs is by adding a peptide that specifically binds to and is taken up by the intended tissue. Such peptides can be found by screening phage display libraries. With in silico, in vitro, and in vivo testing, the peptides that bind the intended tissue most efficiently and most specifically can be identified.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. h.heemskerk@ich.ucl.ac.uk
authors.forename: Hans
authors.initials: H
authors.lastname: Heemskerk
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D019151:Peptide Library; D010455:Peptides