Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells

Vysochinskaya, Vera; Shishlyannikov, Sergey M.; Zabrodskaya, Yana A.; Shmendel, Elena V.; Клотченко, С. А.; Dobrovolskaya, Olga; Gavrilova, N. M.; Makarova, D.; Plotnikova, Marina; Elpaeva, Ekaterina; Горшков, А. Н.; Moshkoff, Dmitry; Маслов, М. А.; Васин, А. В.

doi:10.3390/pharmaceutics15010008

Cited by 13 publications

(19 citation statements)

References 33 publications

(64 reference statements)

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“…DOPE, a zwitterionic lipid, is added for its fusiogenic property, which promote endosomal escape of siRNA into the intracellular compartment [37]. Our previous findings demonstrate that an increase in the proportion of DOPE in liposome formulations, based on 2X3, enhances the efficiency of mRNA delivery to eukaryotic cells [38]. The addition of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG 2000 ) plays a significant role in achieving efficient nuclease protection of siRNA and prolonged drug release of the PEGylated lipoplexes [39].…”

Section: Resultsmentioning

confidence: 99%

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cellsin vitro

Vysochinskaya,

Zabrodskaya,

Dovbysh

et al. 2023

Preprint

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Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs againstBCR-ABL, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model.The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2X3-DOPE-DSPE-PEG2000(0.62% mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

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Section: Resultsmentioning

confidence: 99%

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cellsin vitro

Vysochinskaya,

Zabrodskaya,

Dovbysh

et al. 2023

Preprint

Self Cite

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“…RNA transfections were performed using 2X3-DOPE (1:3) Reagent [9]. RNA complexes were formed in serum-free medium by mixing 0.73 µl of 2X3-DOPE (1:3) reagent and 100 ng synthetic mRNA per well of 96-well plate or 300 ng per well of 12-well plate.…”

Section: Cell Transfectionmentioning

confidence: 99%

Evaluation of the antiviral effect of exogenous human IFN-lambda mRNA against influenza virus in vitro

Plotnikova

Klotchenko

Lozhkov

et al. 2022

Preprint

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Objective: Despite the fact that exogenous mRNA has great prospects for the development of therapeutic medicine, its use is still limited. As the immediate protein precursor, positive-stranded mRNA may represent a suitable alternative to prevent of viral infections. Results: Here, we focused our efforts on making the exogenous RNA encoding human interferon lambda (hIFN-λ1). Using the in vitro transcription method, we obtained hIFN-λ1 RNA and showed that it is capable to rapid translation in transfected cells. We compared the translation efficiency of mRNAs containing unmodified and modified (pseudouridine and 5-methyl-cytidine) nucleosides. Our results showed that the level of hIFN-λ1 during translation from containing modified nucleosides mRNA was 10-fold or more times higher compare to unmodified mRNA. We found that the delivery of exogenous mRNA encoding GFP and hIFN-λ1 in cells resulted in an increase of MDA5, MxA, OAS-1, and IFN-αexpression, which indicate to the activation of innate immune response. At last it was shown that mRNA encoding hIFN-λ1 significantly reduced the reproduction of A/California/07/09 (H1N1pdm09) in comparison with the nonspecific mRNA encoding GFP.

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“…1−3 Among them, cationic liposomes with the ability of cationic lipids to bind RNAs are frequently used for nucleic acid delivery. 4 However, cationic liposomes also cause cytotoxicity by electrostatic binding to the cell membrane, which seriously compromises the results of clinical trials. To solve this problem, researchers conjugated PEG chains to lipids, obtained poly(ethylene glycol) (PEG)-lipid derivatives, and prepared PEGylated cationic liposomes with PEG chains.…”

Section: Introductionmentioning

confidence: 99%

“…Lipid nanoparticles are promising nanomedicine delivery vehicles that have recently gained much attention because of their remarkable success as a delivery platform for COVID-19 mRNA vaccines. − Among them, cationic liposomes with the ability of cationic lipids to bind RNAs are frequently used for nucleic acid delivery . However, cationic liposomes also cause cytotoxicity by electrostatic binding to the cell membrane, which seriously compromises the results of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Cleavable-Branched Polymer-Modified Liposomes Reduce Accelerated Blood Clearance and Enhance Photothermal Therapy

Sui

Wang

Sun

et al. 2023

ACS Appl. Mater. Interfaces

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In recent years, cationic liposomes have been successfully used as delivery platforms for mRNA vaccines. Poly(ethylene glycol) (PEG)-lipid derivatives are widely used to enhance the stability and reduce the toxicity of cationic liposomes. However, these derivatives are often immunogenic, triggering the rise of anti-PEG antibodies. Understanding the role and impact of PEG-lipid derivatives on PEGylated cationic liposomes is key to solving the PEG dilemma. In this study, we designed linear, branched, and cleavable-branched cationic liposomes modified with PEG-lipid derivatives and investigated the effect of the liposome-induced accelerated blood clearance (ABC) phenomenon on photothermal therapy. Our study indicated that the linear PEG-lipid derivatives mediated the effect of photothermal therapy by stimulating splenic marginal zone (MZ) B cells to secrete anti-PEG antibodies and increasing the level of IgM expression in the follicular region of the spleen. However, the cleavable-branched and branched PEG-lipid derivatives did not activate the complement system and avoided the ABC phenomenon by inducing noticeably lower levels of anti-PEG antibodies. The cleavable-branched PEGylated cationic liposomes improved the effect of photothermal therapy by reversing the charge on the liposome surface. This detailed study of PEG-lipid derivatives contributes to the further development and clinical application of PEGylated cationic liposomes.

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Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells

Cited by 13 publications

References 33 publications

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cellsin vitro

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cellsin vitro

Evaluation of the antiviral effect of exogenous human IFN-lambda mRNA against influenza virus in vitro

Cleavable-Branched Polymer-Modified Liposomes Reduce Accelerated Blood Clearance and Enhance Photothermal Therapy

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