Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics

Berber, Burak; Aydın, Cihan; Kocabaş, Fatih; Güney-Esken, Gülen; Yılancıoğlu, Kaan; Karadag-Alpaslan, Medine; Çaliseki, Mehmet; Yuce, Melek; Demir, Sevda; Taştan, Cihan

doi:10.1038/s41434-020-00209-7

Cited by 38 publications

(30 citation statements)

References 140 publications

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“…43 Research in COVID-19 is rapidly expanding. First approaches for siRNA treatment have been described 44 but to the best of our knowledge our study as summarized in Figure S7 is the first which aimed not only to evaluate the antiviral efficiency of siRNAs targeting the SARS-CoV-2 genome but also sought to overcome possible bottlenecks of a therapeutic SARS-CoV-2 siRNA approach.…”

Section: Discussionmentioning

confidence: 99%

Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation

Khaitov

Nikonova

Shilovskiy

et al. 2021

Allergy

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Background: First vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo.Methods: To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used. The most potent siRNA, siR-7, was modified by Locked nucleic acids (LNAs) to obtain siR-7-EM with increased stability and was formulated with the peptide dendrimer KK-46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation -siR-7-EM/KK-46. Using the Syrian Hamster model for SARS-CoV-2 infection the antiviral capacity of siR-7-EM/KK-46 complex was evaluated. Results:We identified the siRNA, siR-7, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro.Moreover, we showed that LNA-modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR-7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR-7-EM/KK-46 in vivo.Conclusions: Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID-19 patients. | 2841KHAITOV eT Al.

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Section: Discussionmentioning

confidence: 99%

Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation

Khaitov

Nikonova

Shilovskiy

et al. 2021

Allergy

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“…Those techniques are based on RNA and can be summarized as CRISPR-Cas12/13-based SHERLOCK, DETECTR, CARVER and PAC-MAN, antisense oligonucleotides, antisense peptide nucleic acids, ribozymes, aptamers, and RNAi silencing. Among those methods ASO or peptide nucleic acid are considered to be the most applicable ones because of the low cost [15] , [35] . Other RNA based techniques for SARS-CoV-2 detections are Nucleic Acid Hybridization Using Microarray and Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) based on cDNA amplified from RNA and Amplicon-Based Metagenomic Sequencing using different sequencing methods such as MinION or Ilumina [35] .…”

Section: Discussionmentioning

confidence: 99%

Challenges to detect SARS-CoV-2 on environmental media, the need and strategies to implement the detection methodologies in wastewaters

Sanchez-Galán

Ureña

Escovar³

et al. 2021

Journal of Environmental Chemical Engineering

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Understanding risks, putting in place preventative methods to seamlessly continue daily activities are essential tools to fight a pandemic. All social, commercial and leisure human activities have an impact on the environmental media. Therefore, to accurately predict the fate and behavior of viruses in the environment, it is necessary to well understand and analyze available detection methods, possible transmission pathways and preventative techniques. The aim of this review is to critically analyze and summarize the research done regarding SARS-COV-2 virus detection, focusing on sampling and laboratory detection methods in environmental media. A special attention will be given to wastewater and sewage sludge. This review has summarized the survival of the virus on surfaces to estimate the risk carried by different environmental media (water, wastewater, air and soil) in order to explain which communities are under higher risk. The critical analysis concludes that the detection of SARS-CoV-2 with current technologies and sampling strategies would reveal the presence of the virus. This information could be used to design systematic sampling points throughout the sewage systems when available, taking into account peak flows and more importantly economic factors on when to sample. Such approaches will be able to provide clues for potential future viral outbreak, saving financial resources by reducing testing necessities for viral detection, hence contributing for more appropriate confinement policies by governments and could be further used to define more precisely post-pandemic or second wave measures if/ when needed.

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“…These novel materials may provide greater utility of biopesticide products in agriculture (Vega-Vásquez et al, 2020), aided by bioengineering and novel production methods to reduce costs or to add unique traits (Hochella et al, 2019), providing benefits across the environmental sciences (Lespes et al, 2020;Li et al, 2020;Slaveykova et al, 2020). Combined all these technological advances support the movement toward that day when FANA biopesticide are used to suppress invasive arthropod pests and insect vectors of pathogens to reduce threats to food security, or health of human and animal populations (Jiang et al, 2019;Adeyinka et al, 2020;Berber et al, 2020;Fletcher et al, 2020;He and Creasey Krainerm, 2020;Huang et al, 2020;Kleter, 2020;Mesterházy et al, 2020;Vega-Vásquez et al, 2020).…”

Section: Future Directionsmentioning

confidence: 99%

Improving Suppression of Hemipteran Vectors and Bacterial Pathogens of Citrus and Solanaceous Plants: Advances in Antisense Oligonucleotides (FANA)

Hunter

Cooper²,

Sandoval-Mojica

et al. 2021

Front. Agron.

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We report on the development, evaluation, and efficient delivery of antisense oligonucleotide FANA (2′-deoxy-2′-fluoro-arabinonucleotide) RNA-targeting technology into citrus trees and potato plants for management of bacterial pathogens and arthropod pests. The FANA ASO technology is a single nucleotide strand of 20–24 nt in length that incorporates 2′F- chemically modifications of nucleotides, along with a phosphorothioate backbone and modified flanking nucleotides, in their structure called “gapmers,” produced by AUM LifeTech., Inc. These unique modified structures of FANA “triggers” enables gymnotic activity that self-delivers into cells, moving systemically in treated plants and insects, with significant suppression of their RNA targets. Reported is the FANA suppression of two plant-infecting bacterium Candidatus Liberibacter asiaticus, CLas (in citrus trees), and C. Liberibacter solanacearum, CLso (in potato and tomato). The CLas pathogen is associated with huanglongbing (a.k.a. Citrus Greening Disease), which causes severe loss of citrus trees, threatening global citrus production. The CLas bacterium is transmitted during feeding by the Asian citrus psyllid, Diaphorina citri (Hemiptera: Liviidae). CLso causes Zebra-Chip disease in potato and is transmitted by the potato psyllid, Bactericera cockerelli (Hemiptera: Triozidae). Infected citrus trees or potato plants were treated with aqueous FANA solutions applied as a soil drench, root-infusion, topical spray, tree trunk injection or by absorption into cuttings, detached leaves, and leaf disks. Plants showed significant reduction of each pathogen or symptom development in response to FANA treatments. Similarly, ingestion of FANA solutions designed specifically to CLas by insects via artificial diets produced significant titer reductions in infected citrus psyllid adults that resulted in reduction of CLas transmission. The unique properties of FANA ASO solves many of the problems of stability, cell entry, and binding affinity that plagues exogenous RNAi strategies. Breakthroughs in production methods are reducing costs enabling these ASO to expand beyond medical applications into agricultural treatments. Thus, FANA ASO may provide viable treatments in the response to crop pandemics, like huanglongbing in citrus that threatens global food production.

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Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics

Cited by 38 publications

References 140 publications

Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation

Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation

Challenges to detect SARS-CoV-2 on environmental media, the need and strategies to implement the detection methodologies in wastewaters

Improving Suppression of Hemipteran Vectors and Bacterial Pathogens of Citrus and Solanaceous Plants: Advances in Antisense Oligonucleotides (FANA)

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