In silico and experimental validation of a new modified arginine-rich cell penetrating peptide for plasmid DNA delivery

[Display omitted] •Argenin-rich chimeric peptide (MR) was designed for plasmid DNA delivery.•Features of MR peptide was evaluated through multiple bioinformatic-based tools.•Protein structures and interaction with DNA was virtually modeled and evaluated.•MR peptide showed outstanding plasmid DNA tra...

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Veröffentlicht in:International journal of pharmaceutics 2022-08, Vol.624, p.122005-122005, Article 122005
Hauptverfasser: Mahjoubin-Tehran, Maryam, Aghaee-Bakhtiari, Seyed Hamid, Sahebkar, Amirhossein, Oskuee, Reza Kazemi, Kesharwani, Prashant, Jalili, Amin
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Sprache:eng
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Zusammenfassung:[Display omitted] •Argenin-rich chimeric peptide (MR) was designed for plasmid DNA delivery.•Features of MR peptide was evaluated through multiple bioinformatic-based tools.•Protein structures and interaction with DNA was virtually modeled and evaluated.•MR peptide showed outstanding plasmid DNA transfection efficiency.•Mechanistically in silico and in vitro studies showed MR peptide may internalize into the cell through endocytosis pathways.•Safety of this nanoparticles was verified through in silico and in vitro studies. Cell-penetrating peptides (CPPs) attracted great attention because of the capability to deliver various types of cargo molecules across into the cells. In this study, we presented a new arginine rich CPP, named MR, for efficient transporting plasmid DNA. We used a combined bioinformatic-based approach to improve the speed and accuracy of CPP evaluation. MR protein properties, structural models, interaction with DNA, as well as cell localization and membrane interaction were evaluated through multiple servers. Importantly, analysis using different algorithms showed the high CPP prediction confidence of MR. Experimental results also revealed the capacity of this gene delivery system in vitro for efficient plasmid DNA transfection. Additionally, in vitro mechanistically studies together with bioinformatic investigation suggested that MR peptide may internalize into the cell through endocytosis pathways. Moreover, in silico safety analysis such as immunogenicity, allergenicity, toxicity, and hemolysis activity as well as MTT assay also confirmed the safety of MR peptide. This study illustrated that MR peptide could be presented as remarkable potential gene delivery system for promising transport of plasmid DNA towards the therapeutic applications.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2022.122005