Nucleic acid-based therapy for coronavirus disease 2019

Piyush, Ravikant; Rajarshi, Keshav; Chatterjee, Aroni; Khan, Rajni; Ray, Shashwati

doi:10.1016/j.heliyon.2020.e05007

Cited by 39 publications

(36 citation statements)

References 156 publications

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“…Recently, mRNA-based vaccines have attracted a lot of attention. Two mRNA vaccines, namely BNT162b2 (developed by Pfizer, New York, NY, USA, in collaboration with BioNtech, Mayence, Germany) and mRNA-1273 (from Moderna, Cambridge, MA, USA, in collaboration with the National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA), reached Phase 3 clinical trial and were authorized for emergency use against SARS-CoV-2 infection by health authorities [ 1 , 2 , 3 ]. Their complete approval would make them the world’s first mRNA-based vaccines authorized for use on humans.…”

Section: Introductionmentioning

confidence: 99%

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

et al. 2021

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The approval of two mRNA vaccines as urgent prophylactic treatments against Covid-19 made them a realistic alternative to conventional vaccination methods. However, naked mRNA is rapidly degraded by the body and cannot effectively penetrate cells. Vectors capable of addressing these issues while allowing endosomal escape are therefore needed. To date, the most widely used vectors for this purpose have been lipid-based vectors. Thus, we have designed an innovative vector called LipoParticles (LP) consisting of poly(lactic) acid (PLA) nanoparticles coated with a 15/85 mol/mol DSPC/DOTAP lipid membrane. An in vitro investigation was carried out to examine whether the incorporation of a solid core offered added value compared to liposomes alone. To that end, a formulation strategy that we have named particulate layer-by-layer (pLbL) was used. This method permitted the adsorption of nucleic acids on the surface of LP (mainly by means of electrostatic interactions through the addition of LAH4-L1 peptide), allowing both cellular penetration and endosomal escape. After a thorough characterization of size, size distribution, and surface charge— and a complexation assessment of each vector—their transfection capacity and cytotoxicity (on antigenic presenting cells, namely DC2.4, and epithelial HeLa cells) were compared. LP have been shown to be significantly better transfecting agents than liposomes through pLbL formulation on both HeLa and DC 2.4 cells. These data illustrate the added value of a solid particulate core inside a lipid membrane, which is expected to rigidify the final assemblies and makes them less prone to early loss of mRNA. In addition, this assembly promoted not only efficient delivery of mRNA, but also of plasmid DNA, making it a versatile nucleic acid carrier that could be used for various vaccine applications. Finally, if the addition of the LAH4-L1 peptide systematically leads to toxicity of the pLbL formulation on DC 2.4 cells, the optimization of the nucleic acid/LAH4-L1 peptide mass ratio becomes an interesting strategy—essentially reducing the peptide intake to limit its cytotoxicity while maintaining a relevant transfection efficiency.

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Section: Introductionmentioning

confidence: 99%

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

et al. 2021

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“…The biomolecular platform for ss-aRNase design may also serve for the development of efficient antiviral agents that could meet the current urgent need for these drugs. Successful studies on the suppression of SARS-CoV, the virus that is highly homologous to SARS-CoV-2, by siRNAs and ribozymes [ 104 , 105 , 106 , 107 ], have inspired researchers to actively develop anti-SARS-CoV-2 antisense drugs. Catching up with current needs, ss-aRNases may be promising candidates for the clinical management of coronaviruses.…”

Section: Discussionmentioning

confidence: 99%

Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences

et al. 2021

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RNA-targeting therapeutics require highly efficient sequence-specific devices capable of RNA irreversible degradation in vivo. The most developed methods of sequence-specific RNA cleavage, such as siRNA or antisense oligonucleotides (ASO), are currently based on recruitment of either intracellular multi-protein complexes or enzymes, leaving alternative approaches (e.g., ribozymes and DNAzymes) far behind. Recently, site-selective artificial ribonucleases combining the oligonucleotide recognition motifs (or their structural analogues) and catalytically active groups in a single molecular scaffold have been proven to be a great competitor to siRNA and ASO. Using the most efficient catalytic groups, utilising both metal ion-dependent (Cu(II)-2,9-dimethylphenanthroline) and metal ion-free (Tris(2-aminobenzimidazole)) on the one hand and PNA as an RNA recognising oligonucleotide on the other, allowed site-selective artificial RNases to be created with half-lives of 0.5–1 h. Artificial RNases based on the catalytic peptide [(ArgLeu)2Gly]2 were able to take progress a step further by demonstrating an ability to cleave miRNA-21 in tumour cells and provide a significant reduction of tumour growth in mice.

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“…Many manuscripts reviewed the possibility of using RNA interference (RNAi) as a therapeutic approach against COVID-19 (Itani et al, 2020;Le et al, 2020;Piyush et al, 2020;Shaffer, 2020;Yu et al, 2020). We also reviewed the siRNA-based strategies used in the past coronavirus infections and the prospects of such strategies in combating SARS-CoV-2 pandemic (Uludag et al, 2020).…”

Section: Antiviral Effectmentioning

confidence: 99%

Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference

Aliabadi

Totonchy

Mahdipoor

et al. 2021

Front. Nanotechnol.

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Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will result in lower viral load and reduced cell death. Two different categories of nucleic acid delivery systems, Peptide/Lipid-Associated Nucleic Acids (PLANAs) and lipophilic polymers, were investigated for their toxicity in human lung fibroblast cells and their ability to deliver specific siRNAs targeting Spike and Envelope proteins in order to prevent cell death in infected cells. Selected siRNAs were effectively delivered to human lung fibroblast cells with negligible toxicity. Cell death due to viral infection was significantly reduced with individual and combinatorial silencing of selected viral proteins. The combinatorial silencing of Spike and Envelope proteins restored the cell viability completely and eliminated plaques in the investigated system. Our cell culture data indicate promising results for the RNAi based approach as an alternative antiviral treatment.

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Nucleic acid-based therapy for coronavirus disease 2019

Cited by 39 publications

References 156 publications

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences

Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference

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