Cell Penetrating Peptide Conjugates of Steric Block Oligonucleotides

Overview

Journal Adv Drug Deliv Rev

Specialty Pharmacology

Date 2007 Nov 27

PMID 18037527

Citations 62

Authors

Bernard Lebleu

Hong M Moulton

Rachida Abes

Gabriela D Ivanova

Said Abes

David A Stein

Patrick L Iversen

Andrey A Arzumanov

Michael J Gait

Affiliations

Soon will be listed here.

Abstract

Charge neutral steric block oligonucleotide analogues, such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligomers (PMO), have promising biological and pharmacological properties for antisense applications, such as for example in mRNA splicing redirection. However, cellular uptake of free oligomers is poor and the utility of conjugates of PNA or PMO to cell penetrating peptides (CPP), such as Tat or Penetratin, is limited by endosomal sequestration. Two new families of arginine-rich CPPs named (R-Ahx-R)(4) AhxB and R(6)Pen allow efficient nuclear delivery of splice correcting PNA and PMO at micromolar concentrations in the absence of endosomolytic agents. The in vivo efficacy of (R-Ahx-R)(4) AhxB PMO conjugates has been demonstrated in mouse models of Duchenne muscular dystrophy and in various viral infections.

Citing Articles

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Structural insights into the morpholino nucleic acid/RNA duplex using the new XNA builder Ducque in a molecular modeling pipeline.

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Antisense oligonucleotide gapmers containing phosphoryl guanidine groups reverse MDR1-mediated multiple drug resistance of tumor cells.

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