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), R9 (nona-arginine), K8 (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 R6 (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.
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August 2007
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Conference Article|
July 20 2007
Cell-penetrating-peptide-based delivery of oligonucleotides: an overview
R. Abes;
R. Abes
*UMR 5235 CNRS, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France
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A.A. Arzumanov;
A.A. Arzumanov
‡Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, U.K.
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H.M. Moulton;
H.M. Moulton
†AVI BioPharma Inc., 4575 SW Research Way, Corvallis, OR 97333, U.S.A.
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S. Abes;
S. Abes
*UMR 5235 CNRS, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France
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G.D. Ivanova;
G.D. Ivanova
‡Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, U.K.
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P.L. Iversen;
P.L. Iversen
†AVI BioPharma Inc., 4575 SW Research Way, Corvallis, OR 97333, U.S.A.
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M.J. Gait;
M.J. Gait
‡Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, U.K.
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B. Lebleu
B. Lebleu
1
*UMR 5235 CNRS, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 5, France
1To whom correspondence should be addressed (email blebleu@univ-montp2.fr).
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Publisher: Portland Press Ltd
Received:
May 08 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 775–779.
Article history
Received:
May 08 2007
Citation
R. Abes, A.A. Arzumanov, H.M. Moulton, S. Abes, G.D. Ivanova, P.L. Iversen, M.J. Gait, B. Lebleu; Cell-penetrating-peptide-based delivery of oligonucleotides: an overview. Biochem Soc Trans 1 August 2007; 35 (4): 775–779. doi: https://doi.org/10.1042/BST0350775
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