Miravirsen (SPC3649) can inhibit the biogenesis of miR-122

Gebert, Luca F. R.; Rebhan, Mario A. E.; Crivelli, Silvia E. M.; Denzler, Rémy; Stoffel, Markus; Hall, Jonathan

doi:10.1093/nar/gkt852

Cited by 310 publications

(208 citation statements)

References 46 publications

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“…The most clinically advanced miRNA-based therapy at the present time is a miR-122 antagonist, SPC3649, that targets an infectious disease-hepatitis C virus-and is currently being evaluated in phase 2 clinical trials [45][46][47] . Other miRNAs currently in development are in the area of cardiovascular disease and include miR-208 (ref.…”

Section: Discussionmentioning

confidence: 99%

MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

et al. 2015

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Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4 þ T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.

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Section: Discussionmentioning

confidence: 99%

MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

et al. 2015

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“…Recently, the clinical trial on BMiravirsen^(SPC3649), a synthetic oligonucleotide complementary to miR-122 which can sequester and inhibit the activity of this miRNA, has been extended to long-term phase 2 study for patients with chronic hepatitis C virus genotype 1 infection [12]. This shows some promise for the successful implementation of currently developed miRNA-based therapeutics for malignant diseases, which currently are still mostly evaluated in early preclinical phases.…”

Section: Introductionmentioning

confidence: 99%

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Florczuk¹,

Szpechcinski²,

Chorostowska‐Wynimko³

2017

Targ Oncol

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Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as nonsmall cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level.

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“…Impressively, in a phase 2 study in patients with chronic HCV infections, treatment with miravirsen resulted in a mean 2-to 3-log decrease in serum HCV RNA, and HCV RNA was below detectable levels in 4 of the 9 treated patients. 114,115 These impressive data were the first to demonstrate that anti-miR oligonucleotide drugs can achieve clinically meaningful efficacy. An even more potent mir-122 drug (RG-101), which contains a GalNAc targeting moiety to increase targeting to the liver, has entered clinical development.…”

Section: Clinical Experience With Mirna Modulatorsmentioning

confidence: 99%

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

MacLeod

Crooke

2017

The Journal of Clinical Pharma

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RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs. Particularly with ASOs, recent clinical data have demonstrated proof of mechanism and clinical benefit with these approaches across several nononcology disease areas by multiple routes of administration. In cancer, next-generation ASOs have recently demonstrated single-agent activity in patients with highly refractory cancers. Here we discuss advances in RNA therapeutics for the treatment of cancer and the challenges that remain to solidify these as mainstay therapeutic modalities to bridge the pharmacogenomic divide that remains in cancer drug discovery.

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Miravirsen (SPC3649) can inhibit the biogenesis of miR-122

Cited by 310 publications

References 46 publications

MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

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