Inhibition of hepatitis C virus replication by single and dual small interfering RNA using an HCV-infected cell model

Xing, Xiaokang; Li, Sujuan; He, Jiliang; Chen, Zhi

doi:10.1007/s10529-011-0761-y

Cited by 10 publications

(4 citation statements)

References 14 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that the blockage of multiple physiological events mediating malignancy and tumor cell survival, or blockage of a single critical path at multiple points to maximize inhibition of that path, is likely to result in greater-than-additive inhibition of tumor cell growth and viability (25). Similarly, in more recent studies, in vitro RNAi experiments conducted against hepatitis C virus using combinatorial treatment with two siRNAs elicited a significant increase in antiviral effects (26).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Gao

et al. 2012

Biomedical Reports

View full text Add to dashboard Cite

Abstract. The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11A gene (BCL11A) encodes a krüppel-like zinc finger protein, which is important in thymopoiesis and has been associated with hematopoietic malignancies. In this study, we investigated whether the downregulation of BCL11A mRNA by small interference RNA (siRNA) was capable of inducing apoptosis, and tested the effect of BCL11A siRNA combined with BCL2 siRNA in B lymphoma cell lines (SUDHL6, EB1). BCL11A siRNA was transfected into SUDHL6, EB1 cells with HiPerfect transfection reagents. After transient transfection with BCL11A siRNA, the expression levels of BCL11A mRNA and protein were assayed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. The cell proliferation was determined by a cell counting kit-8 (CCK8) assay. Apoptosis was determined by morphological observation and flow cytometric analysis. The results showed that the expression levels of BCL11A mRNA and protein from SUDHL6, EB1 cells transfected with BCL11A siRNA decreased, compared with either the scrambled negative control siRNA group or untransfected cells group (P<0.05). Viability of cells transfected with BCL11A siRNA was less compared to cells transfected with control siRNA and untransfected SUDHL6, EB1 cells, respectively (P<0.05). BCL11A siRNA induced apoptosis in both SUDHL6 and EB1 cells. BCL11A siRNA combined with BCL2 siRNA significantly inhibited cell growth. Apoptotic rates of SUDHL6, EB1 cells treated with BCL11A siRNA combined with BCL2 siRNA significantly increased (P<0.05), compared with either the scrambled control (Sc) siRNA and BCL2 siRNA combination or BCL2 or BCL11A siRNA-treated cells alone. Findings of this study suggest the downregulation of BCL11A mRNA by siRNA was able to induce apoptosis.Moreover, BCL11A siRNA combined with BCL2 siRNA increased apoptosis in SUDHL6, EB1 cells. Thus, suppression of BCL11A expression may be a useful approach in the treatment of B lymphoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Gao

et al. 2012

Biomedical Reports

View full text Add to dashboard Cite

show abstract

“…HCV, as a single plus RNA virus that replicates in the cytoplasm of liver cells, is sensitive to RNAi and might be an ideal target for this therapy. Destruction of HCV RNA could induce failure of HCV replication, indicating that the use of siRNA could be a novel regulatory approach for molecular therapeutics 14 15 16 17 . HCV is also prone to mutation and escape from single antivirals, so it also applies to siRNAs and it is generally accepted that combinatorial approaches, or targeting of host dependency factors, are required to prevent emergence of escape mutants.…”

mentioning

confidence: 99%

Target delivery of small interfering RNAs with vitamin E-coupled nanoparticles for treating hepatitis C

Duan

Yan

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

RNA interference (RNAi) represents a promising strategy for the treatment of HCV infection. However, the development of an effective system for in vivo delivery of small interfering RNA (siRNA) to target organ remains a formidable challenge. Here, we develop a unique nanoparticle platform (VE-DC) composed of α-tocopherol (vitamin E) and cholesterol-based cationic liposomes (DOTAP-Chol) for systemic delivery of siRNAs to the liver. A HCV-replicable cell line, Huh7.5.1-HCV, and a transient HCV core expressing cell line, Huh7.5.1-Core, were constructed and used to assess the in vitro anti-HCV activity of VE-DC/siRNAs. A transient in vivo HCV model was also constructed by hydrodynamic injection of pCDNA3.1(+)-3FLAG-Core (pCore-3FLAG) plasmid expressing core protein or pGL3-5′UTR-luciferase (pGL3-5′UTR-luc) plasmid expressing luciferase driven by HCV 5′UTR. Nanoscale VE-DC/siRNA was intravenously injected to assess the liver-targeting property as well as antiviral activity. The nanoscale VE-DC effectively exerted an anti-HCV activity in the in vitro cell models. Post-administration of VE-DC/siRNAs also effectively delivered siRNAs to the liver, suppressing core protein production and firefly luciferase activity, without inducing an innate immunity response or off-target and toxicity effects. The VE-DC platform has high potential as a vehicle for delivery of siRNAs to the liver for gene therapy for targeting hepatitis C.

show abstract

“…Jackson and colleagues suggested that using multiple siRNA duplexes to silence the target gene increased the likelihood of observing the desired phenotype and expression pattern [ 60 ]. This approach was validated by Xing et al, who demonstrated synergistic inhibitory effects on viral replication through the use of dual siRNAs directed against distinct regions of hepatitis C virus genes, achieving superior outcomes at lower doses compared to those achieved with single siRNA treatment [ 172 ]. In contrast, Haasnoot et al cautioned that excessive influx of multiple siRNAs may lead to increased off-target effects and toxicity by saturating RNAi pathways [ 173 ].…”

Section: Challenges Of Sirna Treatments For Viral Infectionsmentioning

confidence: 99%

Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges

Kang,

Ga,

Kim

et al. 2023

J Biomed Sci

View full text Add to dashboard Cite

RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the COVID-19 pandemic. Since their development in the 1990s, RNA interference (RNAi) therapeutics have demonstrated potential in reducing the expression of disease-associated genes. Nucleic acid‐based therapeutics, including RNAi therapies, that degrade viral genomes and rapidly adapt to viral mutations, have emerged as alternative treatments. RNAi is a robust technique frequently employed to selectively suppress gene expression in a sequence-specific manner. The swift adaptability of nucleic acid‐based therapeutics such as RNAi therapies endows them with a significant advantage over other antiviral medications. For example, small interfering RNAs (siRNAs) are produced on the basis of sequence complementarity to target and degrade viral RNA, a novel approach to combat viral infections. The precision of siRNAs in targeting and degrading viral RNA has led to the development of siRNA-based treatments for diverse diseases. However, despite the promising therapeutic benefits of siRNAs, several problems, including impaired long-term protein expression, siRNA instability, off-target effects, immunological responses, and drug resistance, have been considerable obstacles to the use of siRNA-based antiviral therapies. This review provides an encompassing summary of the siRNA-based therapeutic approaches against viruses while also addressing the obstacles that need to be overcome for their effective application. Furthermore, we present potential solutions to mitigate major challenges.

show abstract

Inhibition of hepatitis C virus replication by single and dual small interfering RNA using an HCV-infected cell model

Cited by 10 publications

References 14 publications

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Target delivery of small interfering RNAs with vitamin E-coupled nanoparticles for treating hepatitis C

Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges

Contact Info

Product

Resources

About