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Cell-penetrating-peptide-based delivery of oligonucleotides: an overview.
|Title||Cell-penetrating-peptide-based delivery of oligonucleotides: an overview.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Abes R, Arzumanov AA, Moulton HM, Abes S, Ivanova GD, Iversen PL, Gait MJ, Lebleu B|
|Journal||Biochemical Society transactions|
|Date Published||2007 Aug|
|Keywords||Animals, Drug Delivery Systems, Humans, Oligonucleotides, Peptides, Protein Sorting Signals, Protein Transport|
Cationic CPPs (cell-penetrating peptides) have been used largely for intracellular delivery of low-molecular-mass drugs, biomolecules and particles. Most cationic CPPs bind to cell-associated glycosaminoglycans and are internalized by endocytosis, although the detailed mechanisms involved remain controversial. Sequestration and degradation in endocytic vesicles severely limits the efficiency of cytoplasmic and/or nuclear delivery of CPP-conjugated material. Re-routing the splicing machinery by using steric-block ON (oligonucleotide) analogues, such as PNAs (peptide nucleic acids) or PMOs (phosphorodiamidate morpholino oligomers), has consequently been inefficient when ONs are conjugated with standard CPPs such as Tat (transactivator of transcription), R(9) (nona-arginine), K(8) (octalysine) or penetratin in the absence of endosomolytic agents. New arginine-rich CPPs such as (R-Ahx-R)(4) (6-aminohexanoic acid-spaced oligo-arginine) or R(6) (hexa-arginine)-penetratin conjugated to PMO or PNA resulted in efficient splicing correction at non-cytotoxic doses in the absence of chloroquine. SAR (structure-activity relationship) analyses are underway to optimize these peptide delivery vectors and to understand their mechanisms of cellular internalization.
|Alternate Journal||Biochem. Soc. Trans.|