Intracellular delivery of nucleic acid by cell‐permeable hPP10 peptide

Ding, Yi; Zhao, Xin; Geng, Jingping; Guo, Xiao; Ma, Jie-Lan; Wang, Hu; Liu, Changbai

doi:10.1002/jcp.27826

Cited by 23 publications

(17 citation statements)

References 23 publications

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“…To further investigate the penetration of Dot1l peptide, the interaction between Dot1l peptide and membrane was predicted using PPM web server and MCPep server. As our previous paper has shown, well-known CPP-TAT [9], hPP3 [19], and hPP10 [20,26] can partially be inserted into the membrane predicted by the PPM web server [27], similar to Dot1l peptide's weak property of membrane insertion ( Figure 4A). The MCPep server, a computational tool for the prediction of peptide (secondary structure) occurrence in lipid bilayers and aqueous environments, was used for further prediction of interactions between Dot1l peptide and membrane.…”

Section: Dot1l Peptide-membrane Interaction Predictionsupporting

confidence: 52%

“…The Dot1l/pDNA complexes with the indicated N/P ratio were mixed in accordance to the protocol established [26,27]. The mean zeta potential and average diameter of the peptide/pDNA complexes were examined by Zetasizer (Zetasize-Nano ZS90; Malvern Instruments, Worcestershire, UK) and data analysis was performed with Zetasizer software 6.30.…”

Section: Zeta-potential and Particle Size Measurementmentioning

confidence: 99%

“…Following the documented procedure and protocol for the penetration property of CPP using in vitro assay [9,26,27], MCF7 cells incubated with FITC-labeled Dot1l peptide (5 µM) for 1 h, without DMSO pretreatment, were examined by fluorescence microscopy. Fluorescence imaging was conducted to examine Dot1l peptide penetrating ability at indicated concentrations (from 2.5 to 10 µM).…”

Section: Penetrating Property Of Dot1l Peptidementioning

confidence: 99%

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Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L

et al. 2020

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Cellular uptake and intracellular release efficiency of biomacromolecules is low because of hurdles in the cell membrane that result in limited access to intra-cellular targets with few functional effects. Cell-penetrating peptides (CPPs) act as cargo delivery vehicles to promote therapeutic molecule translocation. Here, we describe the novel CPP-Dot1l that not only penetrates by itself, but also mediates cargo translocation in cultured cells, as confirmed by fluorescence microscopy and fluorescence spectrophotometry. We conducted cytotoxicity assays and safety evaluations, and determined peptide-membrane interactions to understand the possible pathway for cargo translocation. Additional nucleic acid and covalently conjugated green fluorescence protein (GFP) studies mediated by CPP-Dot1l were conducted to show functional delivery potential. Results indicate that CPP-Dot1l is a novel and effective CPP due to its good penetrating properties in different cell lines and its ability to enter cells in a concentration-dependent manner. Its penetration efficiency can be prompted by DMSO pretreatment. In addition, not only can it mediate plasmid delivery, but CPP-Dot1l can also deliver GFP protein into cytosol. In conclusion, the findings of this study showed CPP-Dot1l is an attractive pharmaceutical and biochemical tool for future drug, regenerative medicine, cell therapy, gene therapy, and gene editing-based therapy development.

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Section: Dot1l Peptide-membrane Interaction Predictionsupporting

confidence: 52%

Section: Zeta-potential and Particle Size Measurementmentioning

confidence: 99%

Section: Penetrating Property Of Dot1l Peptidementioning

confidence: 99%

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Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L

et al. 2020

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“…Another study also showed that hPP10 could mediate Cre fusion protein delivery and pDNA transfection simultaneously in the Cre/loxp system in vitro. Furthermore, hPP10 fused with an RNA-binding domain could deliver small interfering RNA into cells to silence the reporter gene expression [171]. On the other hand, hPP3 (KPKRKRRKKKGHGWSR) derived from human nuclear body protein could enter cells in vitro, at a concentration-, incubation time-, serum-and temperature-dependent manner [172].…”

Section: Peptide and Protein Deliverymentioning

confidence: 99%

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Kardani

Milani

Shabani

et al. 2019

Expert Opinion on Drug Delivery

152

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Introduction: Cell penetrating peptides (CPPs) known as protein translocation domains (PTD), membrane translocating sequences (MTS), or Trojan peptides (TP) are able to cross biological membranes without clear toxicity using different mechanisms, and facilitate the intracellular delivery of a variety of bioactive cargos. CPPs could overcome some limitations of drug delivery and combat resistant strains against a broad range of diseases. Despite delivery of different therapeutic molecules by CPPs, they lack cell specificity and have a short duration of action. These limitations led to design of combined cargo delivery systems and subsequently improvement of their clinical applications. Areas covered: This review covers all our studies and other researchers in different aspects of CPPs such as classification, uptake mechanisms, and biomedical applications. Expert opinion: Due to low cytotoxicity of CPPs as compared to other carriers and final degradation to amino acids, they are suitable for preclinical and clinical studies. Generally, the efficiency of CPPs was suitable to penetrate the cell membrane and deliver different cargos to specific intracellular sites. However, no CPP-based therapeutic approach has approved by FDA, yet; because there are some disadvantages for CPPs including short half-life in blood, and nonspecific CPP-mediated delivery to normal tissue. Thus, some methods were used to develop the functions of CPPs in vitro and in vivo including the augmentation of cell specificity by activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, incorporation of CPPs into multifunctional dendrimeric or liposomal nanocarriers to improve selectivity and efficiency especially in tumor cells.

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“…However, nucleic acids are large and hydrophilic, meaning they are not able to cross cell membranes [29]. To overcome this problem, different vectors have been used but most of them, especially viral particles, display a high toxicity [70]. It is now known that cationic CPPs, such as TAT [61] or hPP10 [70], can be bound in a covalent or non-covalent fashion to unprotected nucleic acids (plasmid DNA and small interfering RNA).…”

Section: Cpps As Molecular Carriers In Cancermentioning

confidence: 99%

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

2019

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Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

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Intracellular delivery of nucleic acid by cell‐permeable hPP10 peptide

Cited by 23 publications

References 23 publications

Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L

Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

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