Peptide-based delivery of nucleic acids: design, mechanism of uptake and applications to splice-correcting oligonucleotides.

TitlePeptide-based delivery of nucleic acids: design, mechanism of uptake and applications to splice-correcting oligonucleotides.
Publication TypeJournal Article
Year of Publication2007
AuthorsAbes S, Moulton HM, Turner J, Clair P, Richard JP, Iversen P, Gait MJ, Lebleu B
JournalBiochemical Society transactions
Volume35
IssuePt 1
Pagination53-5
Date Published2007 Feb
ISSN0300-5127
KeywordsAlternative Splicing, Cell Membrane, Cell Nucleus, Cytoplasm, Drug Delivery Systems, Gene Transfer Techniques, Genetic Therapy, Genomics, Humans, Models, Biological, Nucleic Acids, Oligonucleotides, Peptides
Abstract

CPPs (cell-penetrating peptides) have given rise to much interest for the delivery of biomolecules such as peptides, proteins or ONs (oligonucleotides). CPPs and their conjugates were initially thought to translocate through the cell membrane by a non-endocytotic mechanism which has recently been re-evaluated. Basic-amino-acid-rich CPPs first interact with cell-surface proteoglycans before being internalized by endocytosis. Sequestration and degradation in endocytotic vesicles severely limits the cytoplasmic and nuclear delivery of the conjugated biomolecules. Accordingly, splicing correction by CPP-conjugated steric-block ON analogues is inefficient in the absence of endosomolytic agents. New arginine-rich CPPs allowing efficient splicing correction by conjugated PNAs (peptide nucleic acids) or PMO (phosphorodiamidate morpholino oligomer) steric blockers in the absence of endosomolytic agents have recently been defined in our group and are currently being characterized. They offer promising leads for the development of efficient cellular delivery vectors for therapeutic steric-block ON analogues.

DOI10.1042/BST0350053
Alternate JournalBiochem. Soc. Trans.