siRNAs: Potential therapeutic agents against Hepatitis C Virus

Ashfaq, Usman Ali; Yousaf, Muhammad; Aslam, Maida; Ejaz, Rahat; Saleem, Sidrah; Ullah, Obaid

doi:10.1186/1743-422x-8-276

Cited by 28 publications

(20 citation statements)

References 61 publications

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“…25 Moreover, in the present study the effect of the p44/42 siRNA to silence p44/42 expression was no longer present at week 2 after the microinjections, consistent with a previous report indicating that the maximal silencing effect of siRNA transfection typically occurs 5-7 days after injection. 26 Viral transfection would likely produce a more widespread and sustained reduction in p44/42 MAPK, with greater impact on the measured variables.…”

Section: Discussionmentioning

confidence: 99%

Early Interference With p44/42 Mitogen-Activated Protein Kinase Signaling in Hypothalamic Paraventricular Nucleus Attenuates Angiotensin II–Induced Hypertension

Xue²,

Zhang³

et al. 2013

Hypertension

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Blood-borne angiotensin II (ANG II) can upregulate p44/42 mitogen-activated protein kinase (MAPK) signaling and ANG II type-1 receptors (AT1R) in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center. We tested the hypothesis that brain p44/42 MAPK signaling contributes to the development of ANG II-induced hypertension. ANG II infusion (120 ng/kg/min, SC) induced increases in phosphorylated p44/42 MAPK and AT1R in the PVN after 1 week, before the onset of hypertension, that were sustained as hypertension developed during a 2- or 3-week infusion protocol. Bilateral PVN microinjections of small interfering RNAs (siRNA) for p44/42 MAPK, at the onset of the ANG II infusion or one week later, prevented the early increase in p44/42 MAPK activity. The early treatment normalized AT1R expression in the PVN and attenuated the hypertensive response to the 2-week infusion of ANG II. The later siRNA microinjections had a transient effect on AT1R expression in PVN and no effect on the hypertensive response to the 3-week infusion of ANG II. The early treatment normalized the pressure response to ganglionic blockade. ANG II also induced increases in mRNA for pro-inflammatory cytokines that were not affected by either siRNA treatment. These results suggest that the full expression of ANG II-induced hypertension depends upon p44/42 MAPK-mediated effects. A potential role for p44/42 MAPK in modulating the ANG II-induced central inflammatory response might also be considered. MAPK signaling in PVN may be a novel target for early intervention in the progression of ANG II-dependent hypertension.

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Section: Discussionmentioning

confidence: 99%

Early Interference With p44/42 Mitogen-Activated Protein Kinase Signaling in Hypothalamic Paraventricular Nucleus Attenuates Angiotensin II–Induced Hypertension

Xue²,

Zhang³

et al. 2013

Hypertension

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“…Importantly, a combination of siRNAs directed against cellular HCV cofactors and the HCV genome had more pronounced effects on suppressing HCV replication than either treatment alone [116,118,121] . The instances of siRNAs targeting cellular factors for antiviral therapy against HCV has been more extensively reviewed in the literature [122,123] .…”

Section: Rnai Against Host Factorsmentioning

confidence: 99%

Prospects for nucleic acid-based therapeutics against hepatitis C virus

Lee

Kim

Lee

2013

WJG

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In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

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“…siRNA is highly specific against target RNA. Therefore, siRNA is an important tool in understanding and discovering the function of gene [35] . siRNA mediated silencing of attachment receptor and clathrin-mediated endocytosis can inhibit DENV entry and multiplication in HepG2 cells, ultimately reducing the viral load.…”

Section: Rnai Against Denvmentioning

confidence: 99%