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Cell-Penetrating Peptides 2016

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 November 2016) | Viewed by 39021

Special Issue Editors


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Guest Editor
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Room 9-153 WDH, Minneapolis, MN 55455, USA
Interests: drug and gene delivery; nanomedicine; biomaterials; pharmacokinetics; stem cells
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2015 Special Issue, “Cell-Penetrating Peptides” (https://www.mdpi.com/journal/ijms/special_issues/cell-penetrating_peptides).

The hydrophobic nature of cell membranes prevents the cellular internalization of exogenous molecules, including different bioactive molecules such as proteins, peptides, and oligonucleotides as well as therapeutics. Discovery of a protein transcription domain that possesses the ability to cross the cell membrane, cell-penetrating peptides (CPPs), has led to a paradigm shift for intracellular delivery of hydrophilic molecules. Since its discovery in the late 1980s, CPPs have been extensively evaluated to assist intracellular delivery of covalently or non-covalently conjugated bioactive cargos, including DNA, siRNA, peptide, protein, liposomes, micelles, nanoparticles, etc. Even though the field of CPPs has advanced rapidly,  there is limited data on the mechanism of cellular entry of CPPs, and it remains as a subject of controversy in the literature. Hence, this Special Issue will focus on the recent advancement of CPPs as a vector for drug and gene delivery, as well as a detailed mechanistic evaluation of CPPs-mediated transmembrane transportation.

Prof. Dr. Jagdish Singh
Dr. Buddhadev Layek
Guest Editor

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Keywords

  • Cell penetrating peptide
  • drug delivery
  • gene delivery
  • endocytosis
  • transport mechanism

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Published Papers (5 papers)

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Research

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1502 KiB  
Communication
Cre Fused with RVG Peptide Mediates Targeted Genome Editing in Mouse Brain Cells In Vivo
by Zhiyuan Zou, Zhaolin Sun, Pan Li, Tao Feng and Sen Wu
Int. J. Mol. Sci. 2016, 17(12), 2104; https://doi.org/10.3390/ijms17122104 - 14 Dec 2016
Cited by 10 | Viewed by 5837
Abstract
Cell penetrating peptides (CPPs) are short peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter) is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the [...] Read more.
Cell penetrating peptides (CPPs) are short peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter) is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the blood-brain barrier (BBB) and enter brain cells. However, whether RVG can be used for genome editing in the brain has not been reported. In this work, we combined RVG with Cre recombinase for bacterial expression. The purified RVG-Cre protein cut plasmids in vitro and traversed cell membranes in cultured Neuro2a cells. By tail vein-injecting RVG-Cre into Cre reporter mouse lines mTmG and Rosa26lacZ, we demonstrated that RVG-Cre could target brain cells and achieve targeted somatic genome editing in adult mice. This direct delivery of the gene-editing enzyme protein into mouse brains with RVG is much safer than plasmid- or viral-based methods, holding promise for further applications in the treatment of various brain diseases. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides 2016)
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Review

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1006 KiB  
Review
Cellular Reprogramming Using Protein and Cell-Penetrating Peptides
by Bong Jong Seo, Yean Ju Hong and Jeong Tae Do
Int. J. Mol. Sci. 2017, 18(3), 552; https://doi.org/10.3390/ijms18030552 - 3 Mar 2017
Cited by 40 | Viewed by 7458
Abstract
Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear transfer technology to direct reprogramming using defined factors, [...] Read more.
Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear transfer technology to direct reprogramming using defined factors, or induced pluripotent stem cells (iPSCs). Considering the ethical issues and efficiency, iPSCs are thought to be one of the most promising stem cells for cell therapy. Induced pluripotent stem cells can be generated by transduction with a virus, plasmid, RNA, or protein. Herein, we provide an overview of the current technology for iPSC generation and describe protein-based transduction technology in detail. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides 2016)
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430 KiB  
Review
The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide
by Hong Kim, Eun-Hye Seo, Seung-Hyun Lee and Bum-Joon Kim
Int. J. Mol. Sci. 2016, 17(12), 2054; https://doi.org/10.3390/ijms17122054 - 7 Dec 2016
Cited by 39 | Viewed by 6396
Abstract
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against [...] Read more.
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides 2016)
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1664 KiB  
Review
CPP-Assisted Intracellular Drug Delivery, What Is Next?
by Junxiao Ye, Ergang Liu, Zhili Yu, Xing Pei, Sunhui Chen, Pengwei Zhang, Meong-Cheol Shin, Junbo Gong, Huining He and Victor C. Yang
Int. J. Mol. Sci. 2016, 17(11), 1892; https://doi.org/10.3390/ijms17111892 - 14 Nov 2016
Cited by 80 | Viewed by 9599
Abstract
For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins [...] Read more.
For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins into cells, thereby denying their clinical potential to become potent anti-cancer drugs. By taking the advantage of the unique cell-translocation property of these short peptides, various payloads of proteins, nucleic acids, or even nanoparticle-based carriers were delivered into all cell types with unparalleled efficiency. However, non-specific CPP-mediated cell penetration into normal tissues can lead to widespread organ distribution of the payloads, thereby reducing the therapeutic efficacy of the drug and at the same time increasing the drug-induced toxic effects. In view of these challenges, we present herein a review of the new designs of CPP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy in combating tumor oncology. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides 2016)
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910 KiB  
Review
The Role of Cell-Penetrating Peptide and Transferrin on Enhanced Delivery of Drug to Brain
by Gitanjali Sharma, Sushant Lakkadwala, Amit Modgil and Jagdish Singh
Int. J. Mol. Sci. 2016, 17(6), 806; https://doi.org/10.3390/ijms17060806 - 25 May 2016
Cited by 75 | Viewed by 8918
Abstract
The challenge of effectively delivering therapeutic agents to brain has led to an entire field of active research devoted to overcome the blood brain barrier (BBB) and efficiently deliver drugs to brain. This review focusses on exploring the facets of a novel platform [...] Read more.
The challenge of effectively delivering therapeutic agents to brain has led to an entire field of active research devoted to overcome the blood brain barrier (BBB) and efficiently deliver drugs to brain. This review focusses on exploring the facets of a novel platform designed for the delivery of drugs to brain. The platform was constructed based on the hypothesis that a combination of receptor-targeting agent, like transferrin protein, and a cell-penetrating peptide (CPP) will enhance the delivery of associated therapeutic cargo across the BBB. The combination of these two agents in a delivery vehicle has shown significantly improved (p < 0.05) translocation of small molecules and genes into brain as compared to the vehicle with only receptor-targeting agents. The comprehensive details of the uptake mechanisms and properties of various CPPs are illustrated here. The application of this technology, in conjunction with nanotechnology, can potentially open new horizons for the treatment of central nervous system disorders. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides 2016)
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