RNA interference in vitro and in vivo using DsiRNA targeting the nucleocapsid N mRNA of human metapneumovirus

Darniot, Magali; Schildgen, Verena; Schildgen, Oliver; Sproat, Brian S.; Kleines, Michael; Ditt, Vanessa; Pitoiset, Cécile; Pothier, Pierre; Manoha, Catherine

doi:10.1016/j.antiviral.2012.01.004

Cited by 23 publications

(17 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These siRNAs had 50% inhibitory concentration (IC 50 ) values in the subnanomolar range. Alternatively, Dicersubstrate siRNAs that target mRNAs of HMPV genes were found to inhibit virus replication in vitro and were partially effective in inhibiting viral replication in mice (70). However, siRNAs generated against glycoprotein (G) mRNA did not result in a reduction in viral growth in A549 cells, even though the G mRNA was significantly reduced (71).…”

Section: Rnaimentioning

confidence: 99%

New Approaches for Immunization and Therapy against Human Metapneumovirus

Wen

Williams

2015

Clin Vaccine Immunol

View full text Add to dashboard Cite

Section: Rnaimentioning

confidence: 99%

New Approaches for Immunization and Therapy against Human Metapneumovirus

Wen

Williams

2015

Clin Vaccine Immunol

View full text Add to dashboard Cite

“…Several researchers used TNFα gene as a target for the treatment of inflammatory and autoimmune diseases [52][53][54]. Murine models are the most popular animal models among various studies that used dsiRNA in vivo [47][48][49][50][51][52][53][54]; however, there are studies where other animal models, for example, rats, were used [53,55]. An exciting example of dsiRNA application was described by Doré-Savard and his colleagues, who demonstrated, for the first time, the efficient suppression of target genes in central nervous system (CNS) of rats by dsiRNA [55].…”

Section: Dicer Substrate Interfering Rnasmentioning

confidence: 99%

“…Several studies use dsiRNA to silence therapeutically relevant genes in vivo (Table 1). Frequently, cancer-related genes and genes of viruses [50,51,[56][57][58][59] are chosen as targets for dsiRNAs [47][48][49]. Several researchers used TNFα gene as a target for the treatment of inflammatory and autoimmune diseases [52][53][54].…”

Section: Dicer Substrate Interfering Rnasmentioning

confidence: 99%

Noncanonical Synthetic RNAi Inducers

Gvozdeva¹,

Chernolovskaya²

2016

RNA Interference

View full text Add to dashboard Cite

This review focuses on current strategies of development of noncanonical synthetic RNA interference (RNAi) inducers with structural modifications for promoting better gene silencing with low risk of side effects. A particular focus is on longer RNA duplexes 25-30 nucleotides (nt) in length that mimic Dicer substrates to improve interaction of RNAi inducers with RNAi machinery. Various design strategies of efficient Dicer substrate smallinterfering RNA (siRNA) are described. It was found that the length, chemical modifications, and overhang structure influence the gene silencing activity and RNA-induced silencing complex (RISC) assembly. Special attention is paid to the long doublestranded RNA duplexes that induce effective gene silencing in Dicer-dependent or Dicerindependent mode. Some structural variants of shorter siRNAs, including hairpin and dumbbell siRNAs and fork-siRNA (fsiRNA) with several nucleotide substitutions at the 3′ end of the sense strand, are also analyzed. These structural modifications provide efficiently increased gene silencing of targets with unfavorable duplex thermodynamic asymmetry. Recent data remove the length and structure limits for the design of RNAi effectors, and add another example in the list of novel RNAi-inducing molecules differing from the classical siRNA, which is discussed in this chapter.

show abstract

“…Similar levels of hMPV suppression were also achieved by Deffrasnes at al. [11] using a comparable siRNA, with an additional study finding that siRNA targeting the N gene resulted in the most consistent antiviral effect [13]. Although a previous study also demonstrated hMPV suppression by RNAi of N and P genes [11], we have employed a uniquely distinct set of N and P targeting siRNA molecules in our study.…”

mentioning

confidence: 99%

“…Previous work has established that in vitro inhibition of the hMPV viral genome can be achieved using siRNA molecules targeting the N and P mRNA of hMPV [11,13]. The viral proteins N and P form part of the hMPV viral replication complex and are critical for viral replication [14], and targeting them via ribonucleic acid interference (RNAi) may be an effective means of viral inhibition [15].…”

mentioning

confidence: 99%

RNAi Targeting of Human Metapneumovirus P and N Genes Inhibits Viral Growth

Nitschinsk¹,

Clarke²,

Idris³

et al. 2018

Intervirology

View full text Add to dashboard Cite

Background/Aims: Human metapneumovirus (hMPV) is an important human respiratory pathogen and is implicated in an array of respiratory illnesses, ranging from asymptomatic infection to severe bronchiolitis. Currently, there is no reliable vaccine or specific antiviral therapy for hMPV infection and treatment is supportive. The use of ribonucleic acid interference has the potential to change that with the targeting of essential viral genes via small interfering RNAs (siRNAs) offering the ability to directly and rapidly treat viral infections. Method: The human lung carcinoma epithelial cell line, A549, was transfected with siRNAs targeting the N and P genes before infecting with hMPV A2 CAN97-83. Viral growth inhibition was then measured by the viral plaque assay and nucleoprotein (N) and phosphoprotein (P) gene knockdown was determined by real-time PCR. Results: In vitro prophylactic use of siRNAs targeting the 3′-abundantly expressed N and P genes of hMPV resulted in potent, sequence-specific viral inhibition. The viral inhibition was specific and not mediated by an anti-viral interferon-β response or cell death. Conclusion: The findings presented here confirmed the highly potent, sequence-specific antiviral effect of siRNAs targeting the N and P gene of hMPV. These results may facilitate the development of a novel therapeutic agent for hMPV control.

show abstract

RNA interference in vitro and in vivo using DsiRNA targeting the nucleocapsid N mRNA of human metapneumovirus

Cited by 23 publications

References 53 publications

New Approaches for Immunization and Therapy against Human Metapneumovirus

New Approaches for Immunization and Therapy against Human Metapneumovirus

Noncanonical Synthetic RNAi Inducers

RNAi Targeting of Human Metapneumovirus <b><i>P</i></b> and <b><i>N</i></b> Genes Inhibits Viral Growth

Contact Info

Product

Resources

About