Publications by authors named "P I Puchkov"

Introduction: Small membrane particles called extracellular vesicles (EVs) transport biologically active cargo between cells, providing intercellular communication. The clinical application of EVs is limited due to the lack of scalable and cost-effective approaches for their production and purification, as well as effective loading strategies.

Methods: Here we used EV mimetics produced by cell treatment with the actin-destabilizing agent cytochalasin B as an alternative to EVs for the delivery of therapeutic nucleic acids.

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Article Synopsis
  • mRNA-based therapies have gained popularity over the last decade, particularly highlighted by their role in mass COVID-19 vaccination, leading to further research into antiviral and anti-cancer vaccines and genetic treatments.
  • Lipid nanoparticles (LNPs) are crucial for mRNA delivery, and adaptable LNP systems are needed to better control how mRNA is taken up and expressed in target cells.
  • New cationic lipid formulations (2X3 and 2X7) have shown effective mRNA delivery in lab cells and live mice, demonstrating prolonged gene activity and localized expression in muscles, pointing to their potential for long-term therapeutic applications.
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The delivery of therapeutic nucleic acids is a prospective method for the treatment of both inherited and acquired diseases including cancer. To achieve maximal delivery efficiency and selectivity, nucleic acids should be targeted to the cells of interest. In the case of cancer, such targeting may be provided through folate receptors overexpressed in many tumor cells.

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Some new polycationic amphiphiles containing a disulfide group were synthesized. Cationic liposomes formed from the compounds synthesized and a helper lipid 1,2-dioleoyl--glycero-3-phosphatidylethanolamine were not toxic for HEK293 and HeLa cells and were highly effective when delivering a fluorescently labeled oligodeoxyribonucleotide. The efficacy of plasmid DNA delivery depended on the cell line and the amphiphile structure, liposomes based on tetracationic amphiphiles being the most effective transfectants.

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Gene therapy requires an effective and safe delivery vehicle for nucleic acids. In the case of non-viral vehicles, including cationic liposomes, the structure of compounds composing them determines the efficiency a lot. Currently, cationic amphiphiles are the most frequently used compounds in liposomal formulations.

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