Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer

Alekseenko, I. V.; Snezhkov, E. V.; Чернов, И. П.; Плешкан, В. В.; Potapov, V. K.; Sass, A. V.; Monastyrskaya, G.S.; Kopantzev, E. P.; Виноградова, Т В; Khramtsov, Yuri V.; Ulasov, A. V.; Rosenkranz, Andrey A.; Соболев, А. С.; Безбородова, О. А.; Plyutinskaya, A. D.; Немцова, Е. Р.; Yakubovskaya, Raisa I.

doi:10.1186/s12967-015-0433-0

Cited by 36 publications

(22 citation statements)

References 102 publications

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“…MPO was fabricated with the adsorption of cations and anions which could significantly decreased the cytotoxicity induced by cations of PEI. The safety of modified PEI was confirmed in a variety of animal experiments [38,39]. The two points above made MPO safety and low toxicity for future clinic application.…”

Section: Discussionmentioning

confidence: 81%

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

Shen

Zhao

Wang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Cerebral infarction is with poorer prognosis and high rates of mortality. After cerebral infarction, the promoting angiogenesis can accelerate the recovery of neurological function. Long non-coding RNA (LncRNA) maternally expressed gene 3 (Meg3) was overexpressed in cerebral infarction area and the knockdown of Meg3 promotes neovascularization and improves nerve function. In this study, we fabricated a nano-polymer wrapped Meg3 short hairpin RNA (ShRNA) plasmid to knockdown Meg3 and conjugated with OX26 antibody (MPO) to realize the brain targeting for the treatment of cerebral infarction. The MPO particle size was 103 ± 11 nm (PDI = 0.27) detected by dynamic light scattering (DLS) and the zeta potential of MPO was -32 mV. MPO achieved brain microvascular endothelial cell (BMEC) targeting and enhanced endothelial cells migration (p < .05), and tube formation (p < .05) in vitro. MPO realized brain tissue target, reduced the volume of cerebral infarction (p < .05) detected by TTC staining, increased capillary density through the HE staining and increased cerebral cortex micro-vessel through immunofluorescence method in vivo. The angiogenesis associated genes Vegfa, and Vegfr2 were upregulated after the treatment of MPO, compared with Meg3 or control plasmid treated group. This study suggested that MPO could achieve brain target and significantly promoted angiogenesis and became a new treatment method for cerebral infarction.

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Section: Discussionmentioning

confidence: 81%

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

Shen

Zhao

Wang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…We previously [ 5 ] showed that the linking of histone H2A with HIV TAT-peptide enhanced the transfection efficiency of histone, likely due to the high positive charge of the peptide, allowing efficient binding to negatively charged cell membranes and subsequent internalization of the complexes. TAT-peptide was also used to enhance the efficiency of polyethyleneimine (PEI)-polyethylene glycol (PEG) copolymer and successfully applied for DNA delivery during suicide gene therapy in a murine tumor model [ 29 ]. Ligands of cell surface receptors that induce their internalization are also frequently used as non-viral carriers.…”

Section: Discussionmentioning

confidence: 99%

Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts

et al. 2020

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Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells.

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“…The expressed cytokine has shown all biological activities of recombinant human IL-12, such as the stimulation of proliferation of the activated natural killer (NK) and T-cells, induction of the interferon-gamma (IFN-γ) secretion by NK and T-cells, and enhancement of lymphokine-activated killer (LAK) activity [89]. There are other constructs simultaneously encoding several cytokines [90,91]. For example, co-expression of IL-2 and tumor necrosis factor (TNF-α), linked by IRES, in an oncolytic adenovirus genome, has allowed increases in the number of CD4 + and CD8 + tumor-infiltrating lymphocytes, as well as T-helper 1 (Th1) and CD86 + dendritic cells (DCs) in vivo [90,92].…”

Section: Multicistronic Vectors For Cancer Therapymentioning

confidence: 99%

Production and Application of Multicistronic Constructs for Various Human Disease Therapies

et al. 2019

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The development of multicistronic vectors has opened up new opportunities to address the fundamental issues of molecular and cellular biology related to the need for the simultaneous delivery and joint expression of several genes. To date, the examples of the successful use of multicistronic vectors have been described for the development of new methods of treatment of various human diseases, including cardiovascular, oncological, metabolic, autoimmune, and neurodegenerative disorders. The safety and effectiveness of the joint delivery of therapeutic genes in multicistronic vectors based on the internal ribosome entry site (IRES) and self-cleaving 2A peptides have been shown in both in vitro and in vivo experiments as well as in clinical trials. Co-expression of several genes in one vector has also been used to create animal models of various inherited diseases which are caused by mutations in several genes. Multicistronic vectors provide expression of all mutant genes, which allows the most complete mimicking disease pathogenesis. This review comprehensively discusses multicistronic vectors based on IRES nucleotide sequence and self-cleaving 2A peptides, including its features and possible application for the treatment and modeling of various human diseases.

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Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer

Cited by 36 publications

References 102 publications

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts

Production and Application of Multicistronic Constructs for Various Human Disease Therapies

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