In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery

Lu, Chi-Jen; Shao, Pei-Lan; Chang, Luan‐Yin; Wang, Jin‐Yuan; Chang, Yi-Hsuan; Lai, Ming Kuen; Chi, Ya‐Hui; Huang, Li‐Min

doi:10.1371/journal.pone.0174523

Cited by 17 publications

(19 citation statements)

References 22 publications

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“…It was observed that shRNAs cloned in pSilencer2.1-U6 puro plasmid vector had a prophylactic effect on the mice infected with A/WSN/33 (H1N1) when delivered as shRNA-jetPEI complex through intra-tracheal route. However, these complexes could not show any therapeutic efficacy [137]. Another study was done on siRNA designed against gene encoding phosphoprotein of RSV.…”

Section: Methods Of Delivery and Challengesmentioning

confidence: 99%

Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

Asha

Kumar

Sanicas³

et al. 2018

JCM

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Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.

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Section: Methods Of Delivery and Challengesmentioning

confidence: 99%

Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

Asha

Kumar

Sanicas³

et al. 2018

JCM

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“…The group of silencers includes antisense oligonucleotides (ASO), ribozymes, DNAzymes, short interfering RNAs (siRNA), microRNAs (miRNAs), short hairpin RNA (shRNAs), or peptide nucleic acids (PNAs). The evidence for their effectiveness in vivo has been provided in many, including those performed in our group [87][88][89][90][91][92]. However, the use of synthetic nucleic acids is limited due to imperfect systems of their introduction into cells.…”

Section: Nanotechnology In Gene Silencing Strategiesmentioning

confidence: 99%

Anti-Influenza Strategies Based on Nanoparticle Applications

2020

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Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic’s history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent need for developing new therapeutics and therapies. Despite the fact that a new generation of universal vaccines or anti-influenza drugs are being developed, the perfect remedy has still not been found. In this review, various strategies for using nanoparticles (NPs) to defeat influenza virus infections are presented. Several categories of NP applications are highlighted: NPs as immuno-inducing vaccines, NPs used in gene silencing approaches, bare NPs influencing influenza virus life cycle and the use of NPs for drug delivery. This rapidly growing field of anti-influenza methods based on nanotechnology is very promising. Although profound research must be conducted to fully understand and control the potential side effects of the new generation of antivirals, the presented and discussed studies show that nanotechnology methods can effectively induce the immune responses or inhibit influenza virus activity both in vitro and in vivo. Moreover, with its variety of modification possibilities, nanotechnology has great potential for applications and may be helpful not only in anti-influenza but also in the general antiviral approaches.

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“…As all siRNAs are not equally potent, various rules have been suggested for the computational prediction, designing, and selection of potential siRNAs. Currently, the siRNA approach has been implemented to inhibit viral replication in cell culture against many viruses like HIV ( Liu et al, 2017 ), Flock house virus (FHV) ( Taning et al, 2018 ), Dengue virus ( Idrees and Ashfaq, 2013 ), Hepatitis C virus (HCV) ( Shahid et al, 2017 ), Influenza virus ( Huang et al, 2017 , Tsai et al, 2018 ), Hepatitis B virus (HBV) ( Wang et al, 2016 ), Human Papillomavirus (HPV) ( Zeng et al, 2017 ) and SARS coronavirus (SARS-CoV) ( Kumar et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

In silico prediction and experimental validation of siRNAs targeting ORF1ab of MERS-CoV in Vero cell line

Sohrab

El‐Kafrawy

Mirza

et al. 2021

Saudi Journal of Biological Sciences

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The Middle East Respiratory Syndrome Coronavirus is well known to cause respiratory syndrome and this virus was identified and isolated for the first time from Jeddah, Saudi Arabia in 2012 from infected patient. In this report, we have conducted the in-silico prediction, designing and evaluation of siRNAs targeting Middle East Respiratory Syndrome Coronavirus orf1ab gene to inhibit the virus replication. By using bioinformatics software, total twenty-one functional, off-target reduced siRNA were selected from four hundred and sixty-two siRNAs based on their greater potency and specificity. We have evaluated only seven siRNAs to analyze their performance and efficacy as antivirals by reverse transfection approach in Vero cells. There was no cytotoxicity of siRNAs at various concentrations was observed in Vero cells. Based on the real-time PCR results, better inhibition of viral replication was observed in the siRNA-1 and 4 as compared to other siRNAs. The results generated from this work provided suitable information about the efficacy of siRNAs which encouraged us to further evaluate the remaining siRNAs to determine their inhibitory effect on the virus replication. We concluded that the insilico prediction and designing resulted in the screening of potential siRNAs with better efficiency, and strength. This can be used to develop oligonucleotide-based antiviral therapeutics against MERS-CoV in the near future.

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In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery

Cited by 17 publications

References 22 publications

Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

Anti-Influenza Strategies Based on Nanoparticle Applications

In silico prediction and experimental validation of siRNAs targeting ORF1ab of MERS-CoV in Vero cell line

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