Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS genes, delivered by hybrid microcarriers

Brodskaia, Aleksandra V.; Timin, Alexander S.; Горшков, А. Н.; Muslimov, Аlbert R.; Бондаренко, А. Б.; Tarakanchikova, Yana V.; Zabrodskaya, Yana A.; Baranovskaya, Irina; Il’inskaja, Eugenia V.; Sakhenberg, E. I.; Sukhorukov, Gleb B.; Васин, А. В.

doi:10.1016/j.antiviral.2018.08.003

Cited by 10 publications

(13 citation statements)

References 49 publications

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“…Furthermore, they can be easily delivered as combinations of siRNAs targeting distinct regions in the same or different viral genes. This will improve the efficacy of the treatment while expanding the spectrum of susceptible genotypes and limiting the emergence of treatment-resistant variants [42]. Therefore, it is not surprising that the number of published clinical studies using siRNAs has increased remarkably in recent years [19].…”

Section: Discussionmentioning

confidence: 99%

siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

2019

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Human respiratory syncytial virus (HRSV) infection is a common cause of severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Both virus replication and the associated inflammatory immune response are believed to be behind these pathologies. So far, no vaccine or effective treatment is available for this viral infection. With the aim of finding new strategies to counteract HRSV replication and modulate the immune response, specific small interfering RNAs (siRNAs) were generated targeting the mRNA coding for the viral fusion (F) protein or nucleoprotein (N), or for two proteins involved in intracellular immune signaling, which are named tripartite motif-containing protein 25 (TRIM25) and retinoic acid-inducible gene-I (RIG-I). Furthermore, two additional bispecific siRNAs were designed that silenced F and TRIM25 (TRIM25/HRSV-F) or N and RIG-I (RIG-I/HRSV-N) simultaneously. All siRNAs targeting N or F, but not those silencing TRIM25 or RIG-I alone, significantly reduced viral titers. However, while siRNAs targeting F inhibited only the expression of the F mRNA and protein, the siRNAs targeting N led to a general inhibition of viral mRNA and protein expression. The N-targeting siRNAs also induced a drastic decrease in the expression of genes of the innate immune response. These results show that both virus replication and the early innate immune response can be regulated by targeting distinct viral products with siRNAs, which may be related to the different role of each protein in the life cycle of the virus.

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Section: Discussionmentioning

confidence: 99%

siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

2019

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“…Multilayered polyelectrolyte carriers, prepared via LbL selfassembly, can be promising tools for siRNA delivery [83,84]. Polycationic polymers, such as PLA [85], PLL [86], PEI [87], PAH [88], chitosan [89], and PLGA [90], were successfully applied for the preparation of non-viral delivery systems of siRNA molecules. Several studies have been performed to knock down green fluorescent protein in cancer cells by the LbL system [12] (Figure 3(b) pDNA).…”

Section: Delivery Of Sirnamentioning

confidence: 99%

Layer-by-Layer technique as a versatile tool for gene delivery applications

Linnik

Tarakanchikova

Zyuzin

et al. 2021

Expert Opinion on Drug Delivery

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Introduction: Gene therapy is a breakthrough medical field which focuses on the therapeutic delivery of recombinant nucleic acids in order to treat or prevent a broad spectrum of diseases. However, a number of important obstacles remain before its wide introduction into clinical practice can be envisaged. One of the biggest bottlenecks is the lack of efficient and safe delivery technologies, particularly, for in vivo distribution. Above and beyond standard requirements for carriers, the delivery systems for gene therapy ideally use a hit-and-run principle (to minimize off-target effect and display of immunogenic moieties). None of the currently used viral vectors fulfills all of these requirements. Therefore, the growing variety of non-viral delivery platforms represents a promising alternative.Areas covered: This review summarizes the Layer-by-Layer (LbL) approaches that can be effectively used for the gene delivery, considering various examples with the transfer of pDNA, mRNA, siRNA as well as genome-editing tools. Ex vivo gene modification of clinically relevant cells and clinical aspects for possible application of LbL systems in gene therapy are also underlined. Expert opinion:The LbL technique provides broad opportunities for the delivery of genetic material for various purposes and offers promise for future clinical application in gene therapy.

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“…A similar principle of cargo protection from premature degradation of the genetic material was shown by Ott et al In this work, silica coating was used to protect the delivered cargo from degradation . Recently, Brodskaia et al employed silica-coated capsules for delivery of a therapeutically relevant siRNA mixture, which can effectively inhibit influenza A virus production . It was shown that such capsules mediate the cellular uptake of siRNA more efficiently than commercially available liposome-based reagents and polyethyleneimine (PEI) and are able to protect siRNA from RNase degradation.…”

Section: Manipulating Cell Fate Using Capsulesmentioning

confidence: 99%

“…Schematic illustration showing the intracellular delivery of biologically active compounds into the cells using multilayer nano- and microcapsules: (A) MDA-MB-231 cells incubated with capsules containing the PEI/DNA complex (reproduced with permission from ref Copyright 2014, Elsevier); (B) delivery of mRNA encoding GFP using silica-coated capsules into HeLa cells (reproduced with permission from ref Copyright 2015, American Chemical Society); (C) capsule internalization in A549 cells and intracellular distribution of fluorescently labeled siRNA (reproduced with permission from ref Copyright 2018, Elsevier); (D) successful transfection of HEK293T with capsules containing the CRISPR-Cas9 system resulting in efficient editing of the dTomato gene (reproduced with permission from ref Copyright 2018, Elsevier); (E) intracellular protein delivery by hollow mesoporous silica capsules with a large surface hole (reproduced with permission from ref Copyright 2012, IOP Publishing).…”

Section: Manipulating Cell Fate Using Capsulesmentioning

confidence: 99%

“…62 Recently, Brodskaia et al employed silica-coated capsules for delivery of a therapeutically relevant siRNA mixture, which can effectively inhibit influenza A virus production. 94 It was shown that such capsules mediate the cellular uptake of siRNA more efficiently than commercially available liposome-based reagents and polyethyleneimine (PEI) and are able to protect siRNA from RNase degradation. Apart from siRNA, mRNA, and DNA, the polymeric capsules are also used to deliver the CRISPR-Cas9 system, the most popular system for gene editing among other tools.…”

Section: ■ Manipulating Cell Fate Using Capsulesmentioning

confidence: 99%

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Multilayer Capsules Inside Biological Systems: State-of-the-Art and Open Challenges

2019

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There are many reports about the interaction of multilayer capsules with biological systems in the literature. A majority of them are devoted to the in vitro study with twodimensional cell cultures. Multilayer capsule fabrication had been under intensive investigation from 1990s and 2000s by Prof. Helmuth Moḧwald, and many of his followers further developed their own research directions, focusing on capsule implementation in various fields of biology and medicine. The aim of this future article is to consistently consider the most recent advances in cell−capsule interactions for different biomedical applications, including functionalization of clinically relevant cells, nonviral gene delivery, magnetization of cells to control their movement, and in vivo drug delivery. Finally, the description and discussion of the new trends and perspectives for improved functionalities of capsules in design and functionalization of cell-assisted drug vehicles are the major topics of this work.

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Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS genes, delivered by hybrid microcarriers

Cited by 10 publications

References 49 publications

siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

Layer-by-Layer technique as a versatile tool for gene delivery applications

Multilayer Capsules Inside Biological Systems: State-of-the-Art and Open Challenges

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