Combining RNA Interference and RIG-I Activation to Inhibit Hepatitis E Virus Replication DOI Creative Commons

Mathias Ziersch,

Dominik Harms, Lena Neumair

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1378 - 1378

Published: Aug. 29, 2024

Hepatitis E virus (HEV) poses a significant global health threat, with an estimated 20 million infections occurring annually. Despite being self-limiting illness, in most cases, HEV infection can lead to severe outcomes, particularly pregnant women and individuals pre-existing liver disease. In the absence of specific antiviral treatments, exploration RNAi interference (RNAi) as targeted strategy provides valuable insights for urgently needed therapeutic interventions against E. We designed small interfering RNAs (siRNAs) HEV, which target helicase domain open reading frame 3 (ORF3). These regions will reduce risk viral escape through mutations, they belong conserved genome. The siRNAs targeting ORF3 efficiently inhibited replication A549 cells after infection. Importantly, siRNA was also highly effective at inhibiting persistently infected cell line, suitable model chronic patients. Furthermore, we showed that 5' triphosphate modification on sense strand activates RIG-I receptor, cytoplasmic pattern recognition receptor recognizes RNA. Upon activation, triggers signaling cascade, effectively suppressing replication. This dual-action strategy, combining activation adaptive immune response inherent pathway, inhibits successfully may development new therapies.

Language: Английский

Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV DOI Creative Commons

Ellen Bowden-Reid,

Ernest Moles, Anthony D. Kelleher

et al.

Drug Delivery and Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Using the knowledge from decades of research into RNA-based therapies, COVID-19 pandemic response saw rapid design, testing and production first ever mRNA vaccines approved for human use in clinic. This breakthrough has been a significant milestone RNA therapeutics vaccines, driving an exponential growth field. The development novel targeting high-threat pathogens, that pose substantial risk to global health, could transform future health delivery. In this review, we provide detailed overview two interference (RNAi) pathways how antiviral RNAi therapies can be used treat acute or chronic diseases caused by viruses SARS-CoV-2 HIV, respectively. We also insights short-interfering (siRNA) delivery systems, with focus on lipid nanoparticles functionalized achieve targeted specific sites disease. review will current developments HIV siRNAs, highlighting strategies advance progression siRNA along clinical pathway. Graphical

Language: Английский

Citations

1
Rational design and structure-activity relationship of random copolymers for enhanced siRNA delivery DOI

Lingshu Li,

Axiang He,

Hongyang Zhao

et al.

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 690, P. 137273 - 137273

Published: March 11, 2025

Language: Английский

Citations

0
SiRNAs as antiviral drugs – Current status, therapeutic potential and challenges. DOI Creative Commons
Trairong Chokwassanasakulkit, Victor B. Oti, Adi Idris

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: unknown, P. 106024 - 106024

Published: Oct. 1, 2024

Language: Английский

Citations

3
Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences DOI Creative Commons
Jianan Sun,

Siya Lu,

Jizhen Xiao

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1072 - 1072

Published: July 3, 2024

Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to development broad-spectrum vaccines and antiviral therapeutics. There remains lack specific therapeutics directly targeting SARS-CoV-2. With ability efficiently inhibit expression target genes in sequence-specific way, small interfering (siRNA) therapy exhibited potential other treatments. In this work, we presented highly effective self-assembled siRNA nanoparticle multiple conserved regions The sequences viral were first screened evaluated their thermodynamic features, off-target effects, secondary structure toxicities. motifs including then designed into nanoparticles. These nanoparticles demonstrated remarkable uniformity stability entered cells through cellular endocytic pathways. Moreover, these effectively inhibited replication SARS-CoV-2, exhibiting superior inhibitory effect compared free siRNA. results that represent candidates for treatment infections, are promisingly against current future variants.

Language: Английский

Citations

2
Combining RNA Interference and RIG-I Activation to Inhibit Hepatitis E Virus Replication DOI Creative Commons

Mathias Ziersch,

Dominik Harms, Lena Neumair

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1378 - 1378

Published: Aug. 29, 2024

Hepatitis E virus (HEV) poses a significant global health threat, with an estimated 20 million infections occurring annually. Despite being self-limiting illness, in most cases, HEV infection can lead to severe outcomes, particularly pregnant women and individuals pre-existing liver disease. In the absence of specific antiviral treatments, exploration RNAi interference (RNAi) as targeted strategy provides valuable insights for urgently needed therapeutic interventions against E. We designed small interfering RNAs (siRNAs) HEV, which target helicase domain open reading frame 3 (ORF3). These regions will reduce risk viral escape through mutations, they belong conserved genome. The siRNAs targeting ORF3 efficiently inhibited replication A549 cells after infection. Importantly, siRNA was also highly effective at inhibiting persistently infected cell line, suitable model chronic patients. Furthermore, we showed that 5' triphosphate modification on sense strand activates RIG-I receptor, cytoplasmic pattern recognition receptor recognizes RNA. Upon activation, triggers signaling cascade, effectively suppressing replication. This dual-action strategy, combining activation adaptive immune response inherent pathway, inhibits successfully may development new therapies.

Language: Английский

Citations

0