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

2007 ◽  
Vol 35 (1) ◽  
pp. 53-55 ◽  
Author(s):  
S. Abes ◽  
H. Moulton ◽  
J. Turner ◽  
P. Clair ◽  
J.P. Richard ◽  
...  

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.

2005 ◽  
Vol 38 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Peter E. Nielsen

1. Introduction 3452. Peptide nucleic acid (PNA) 3463. ‘Cell penetrating peptides’ (CPPs) 3464. Endosomal escape 3475. Cellular delivery of PNA 3476.In vivobioavailability of PNA 3497. References 350Recent results on the cellular delivery of antisense peptide nucleic acids (PNA) via peptide conjugation is briefly discussed, in particular in the context of endosomal entrapment and escape.


2016 ◽  
Vol 31 (3) ◽  
pp. 975-988 ◽  
Author(s):  
Carmen Juks ◽  
Annely Lorents ◽  
Piret Arukuusk ◽  
Ülo Langel ◽  
Margus Pooga

2017 ◽  
Vol 9 ◽  
pp. 162-169 ◽  
Author(s):  
Bénédicte Ndeboko ◽  
Narayan Ramamurthy ◽  
Guy Joseph Lemamy ◽  
Catherine Jamard ◽  
Peter E. Nielsen ◽  
...  

Biopolymers ◽  
2021 ◽  
Author(s):  
Nikita Brodyagin ◽  
Yuka Kataoka ◽  
Ilze Kumpina ◽  
Dennis W. McGee ◽  
Eriks Rozners

2019 ◽  
Vol 15 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Jihui Tang ◽  
Jie Ning ◽  
Xiaoyan Liu ◽  
Baoming Wu ◽  
Rongfeng Hu

<P>Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. </P><P> Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening. </P><P> Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%. </P><P> Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.</P>


2005 ◽  
Vol 390 (2) ◽  
pp. 407-418 ◽  
Author(s):  
Catherine de Coupade ◽  
Antonio Fittipaldi ◽  
Vanessa Chagnas ◽  
Matthieu Michel ◽  
Sophie Carlier ◽  
...  

Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell® peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell® peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell® peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.


2012 ◽  
Vol 158 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Astrid Subrizi ◽  
Eva Tuominen ◽  
Alex Bunker ◽  
Tomasz Róg ◽  
Maxim Antopolsky ◽  
...  

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