scholarly journals Development of Cell Penetrating Peptides for Effective Delivery of Recombinant Factors into Target Cells

2020 ◽  
Vol 27 (11) ◽  
pp. 1092-1101
Author(s):  
Ubashini Vijakumaran ◽  
Fazlina Nordin ◽  
Zariyantey Abdul Hamid ◽  
Maha Abdullah ◽  
Tye Gee Jun
Keyword(s):  
Cell Membrane ◽  
Protective Layer ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Cell Penetrating ◽  
Effective Delivery ◽  
Natural And Synthetic

The cell membrane is a protective layer that strictly controls the passage of molecules restricting the delivery of biomolecules such as drugs, oligonucleotides, peptides, and siRNA into the cells. This shortcoming has been overcome by the discovery of Cell-Penetrating Peptides (CPPs) that has undergone 30 years of evolution. To date, CPPs are largely modified to improve its efficacy and to suit the different delivery applications. The modes of CPPs penetration are still an unresolved mystery and requires further investigations to increase its effectiveness and to diversify its use. Despite having huge potential as a biomolecule carrier, CPPs also have some drawbacks. In this review, the natural and synthetic CPPs, the modifications that have been conducted on CPPs to improve its efficacy, its extended applications, modes of penetration and limitation as well as challenges will be discussed.

scholarly journals Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules

2005 ◽  
Vol 390 (2) ◽  
pp. 407-418 ◽  
Author(s):  
Catherine de Coupade ◽  
Antonio Fittipaldi ◽  
Vanessa Chagnas ◽  
Matthieu Michel ◽  
Sophie Carlier ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Mammalian Cells ◽  
Heparan Sulphate ◽  
Intracellular Delivery ◽  
Membrane Lipid ◽  
Cell Penetrating Peptides ◽  
Heparin Binding ◽  
Independent Manner ◽  
Cell Penetrating

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.

scholarly journals Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

2019 ◽  
Vol 10 (4) ◽  
pp. 45 ◽  
Author(s):  
Anderson ◽  
Hobbs ◽  
Gwenin ◽  
Ball ◽  
Bennie ◽  
...  
Keyword(s):  
Magnetic Nanoparticle ◽  
Genetically Modified ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Tumour Site ◽  
Enzyme Prodrug Therapy ◽  
Delivery Vector ◽  
Cell Penetrating ◽  
Subsequent Activation ◽  
Potential Use

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.

scholarly journals Cell penetrating peptides can exert biological activity: a review

2010 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Jamie Brugnano ◽  
Brian C. Ward ◽  
Alyssa Panitch
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Cell Membrane ◽  
Recent Literature ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
Different Cell Types ◽  
Traditional Understanding

AbstractCell penetrating peptides (CPPs) have been successful in delivering cargo into many different cell types and are an important alternative to other methods of permeation that might damage the integrity of the cell membrane. The traditional view of CPPs is that they are inert molecules that can be successfully used to deliver many cargos intracellularly. The goal of this review is to challenge this traditional understanding of CPPs. Recent literature has demonstrated that CPPs themselves can convey biological activity, including the alteration of gene expression and inhibition of protein kinases and proteolytic activity. Further characterization of CPPs is required to determine the extent of this activity. Research into the use of CPPs for intracellular delivery should continue with investigators being aware of these recent results.

scholarly journals The Utilization of Cell-Penetrating Peptides in the Intracellular Delivery of Viral Nanoparticles

Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2671 ◽  
Author(s):  
Jana Váňová ◽  
Alžběta Hejtmánková ◽  
Marie Hubálek Kalbáčová ◽  
Hana Španielová
Keyword(s):  
Genetic Material ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Current State ◽  
Cargo Delivery ◽  
Viral Particles ◽  
Cell Penetrating ◽  
Viral Nanoparticles ◽  
Immunogenic Properties

Viral particles (VPs) have evolved so as to efficiently enter target cells and to deliver their genetic material. The current state of knowledge allows us to use VPs in the field of biomedicine as nanoparticles that are safe, easy to manipulate, inherently biocompatible, biodegradable, and capable of transporting various cargoes into specific cells. Despite the fact that these virus-based nanoparticles constitute the most common vectors used in clinical practice, the need remains for further improvement in this area. The aim of this review is to discuss the potential for enhancing the efficiency and versatility of VPs via their functionalization with cell-penetrating peptides (CPPs), short peptides that are able to translocate across cellular membranes and to transport various substances with them. The review provides and describes various examples of and means of exploitation of CPPs in order to enhance the delivery of VPs into permissive cells and/or to allow them to enter a broad range of cell types. Moreover, it is possible that CPPs are capable of changing the immunogenic properties of VPs, which could lead to an improvement in their clinical application. The review also discusses strategies aimed at the modification of VPs by CPPs so as to create a useful cargo delivery tool.

scholarly journals Generalized displacement of DNA- and RNA-binding factors mediates the toxicity of arginine-rich cell-penetrating peptides

2018 ◽  
Author(s):  
V. Lafarga ◽  
O. Sirozh ◽  
I. Díaz-López ◽  
M. Hisaoka ◽  
E. Zarzuela ◽  
...  
Keyword(s):  
Dna Binding ◽  
Nucleic Acids ◽  
Rna Binding ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Dna And Rna ◽  
Cell Penetrating ◽  
Dna Binding Factors ◽  
Dna Replication And Repair ◽  
Rna And Dna

ABSTRACTDue to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic-lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids such as RNA transcription, translation, splicing and degradation or DNA replication and repair are impaired by the presence of the CPP. Interestingly, the effects of (PR)n are fully mimicked by PROTAMINE, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated to the onset of ALS.

The world of cell penetrating: the future of medical applications

2020 ◽  
Vol 12 (15) ◽  
pp. 1431-1446 ◽  
Author(s):  
Annarita Falanga ◽  
Lucia Lombardi ◽  
Emilia Galdiero ◽  
Valentina Del Genio ◽  
Stefania Galdiero
Keyword(s):  
Biomedical Applications ◽  
Cell Penetrating Peptides ◽  
Medical Applications ◽  
Critical Factors ◽  
Uptake Mechanism ◽  
Cell Penetrating ◽  
Effective Delivery ◽  
A Cell

Cell-penetrating peptides present huge biomedical applications in a variety of pathologies, thanks to their ability to penetrate membranes and carry a variety of cargoes inside cells. Progress in peptide synthesis has produced a greater availability of virtually any synthetic peptide, increasing their attractiveness. Most molecules when associated to a cell-penetrating peptides can be delivered into a cell, however, understanding of the critical factors influencing the uptake mechanism is of paramount importance to construct nanoplatforms for effective delivery in vitro and in vivo in medical applications. Focus is now on the state-of-art of the mechanisms enabling therapeutics/diagnostics to reach the site target of their activities, and in support of scientists developing platforms for drug delivery and personalized therapies.

scholarly journals Intracellular delivery of therapeutic antibodies into specific cells using antibody-peptide fusions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Julie Gaston ◽  
Nicolas Maestrali ◽  
Guilhem Lalle ◽  
Marie Gagnaire ◽  
Alessandro Masiero ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Penetrating Peptides ◽  
Therapeutic Modality ◽  
Therapeutic Antibodies ◽  
Cell Penetration ◽  
C Terminus ◽  
Macromolecular Drugs ◽  
Cell Penetrating ◽  
Intracellular Compartments ◽  
Intracellular Targets

AbstractBecause of their favorable properties as macromolecular drugs, antibodies are a very successful therapeutic modality for interfering with disease-relevant targets in the extracellular space or at the cell membrane. However, a large number of diseases involve cytosolic targets and designing antibodies able to efficiently reach intracellular compartments would expand the antibody-tractable conditions. Here, we genetically fused cell penetrating peptides (CPPs) at various positions to an antibody targeting cancer cells, evaluated the developability features of the resulting antibody-peptide fusions and the ability of selected constructs to reach the cytosol. We first determined positions in the IgG structure that were permissive to CPP incorporation without destabilizing the antibody. Fusing CPPs to the C-terminus of the light chain and either before or after the hinge had the least effect on antibody developability features. These constructs were further evaluated for cell penetration efficiency. Two out of five tested CPPs significantly enhanced antibody penetration into the cytosol, in particular when fused before or after the hinge. Finally, we demonstrate that specific antibody binding to the cell surface target is necessary for efficient cell penetration of the CPP-antibody fusions. This study provides a solid basis for further exploration of therapeutic antibodies for intracellular targets.

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 ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Membrane ◽  
Cell Surface ◽  
Nucleic Acids ◽  
Peptide Nucleic Acids ◽  
Basic Amino Acid ◽  
Cell Penetrating Peptides ◽  
Cellular Delivery ◽  
Cell Penetrating ◽  
Design Mechanism

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.

Sign in / Sign up

Export Citation Format

Share Document