Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients

Ree, Meike H. van der; Meer, Adriaan J. van der; Bruijne, Joep de; Maan, Raoel; Vliet, André van; Welzel, Tania M.; Zeuzem, Stefan; Lawitz, Eric; Rodrı́guez-Torres, Maribel; Kupčová, V.; Wiercińska-Drapało, A; Hodges, Michael R.; Janssen, Harry L A; Reesink, H. W.

doi:10.1016/j.antiviral.2014.08.015

Cited by 163 publications

(99 citation statements)

References 33 publications

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“…Due to their chemical properties LNA-modified-oligonucleotides are stable in body fluids what facilitates their systemic delivery. Moreover, clinical trials indicated their clinical feasibility and safety in humans [14, 15]. …”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

et al. 2016

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BackgroundEndometrial cancer is the most common cancer of the female reproductive tract.Based on our previous studies we speculated that miR-92a exhibited pro-oncogenic properties in endometrial cancer, and therefore its inhibition could be used as a therapeutic measure in this disease. Therefore in the present study we aimed to investigate both in vitro and in vivo if inhibition of miR-92a in endometrial cancer would limit cancer cells proliferation.MethodsmiR-92a expression was evaluated in four endometrial cancer cell lines using qPCR. Inhibition of miR-92a activity was obtained in endometrial cancer cell lines by a transient transfection of a custom designed Locked Nucleic Acid (LNA)-Inhibitor, developed to work both in vitro and in vivo. In vitro proliferation studies were performed using xCELLigence RTCA DP system. In vivo experiment was performed in Cby.Cg-Foxn1 < nu>/cmdb mice bearing endometrial cancer xenografts, which were intraperitoneally injected with nine dosages of 25 mg/kg of miR-205-LNA-inhibitor.ResultsqPCR revealed increased expression of miR-92a in HEC-1-B, Ishikawa and AN3CA cells. LNA-i-miR-92a inhibited endometrial cancer growth in vitro. It was also demonstrated that systemic administration of LNA-i-miR-92a was feasible and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals, however the effect was observed until 12th experimental day and the last three dosages did not maintain the attenuating effect with the acceleration of tumor growth observed at the end and after cessation of the intraperitoneal therapy.ConclusionsTaken together, these results indicate that intraperitoneal delivery of miR-92a-LNA-modified-inhibitor is feasible, devoid of significant toxicity and moderately inhibits endometrial cancer growth in vivo, and therefore warrants further studies investigating other routes of inhibitor delivery possibly in other animal models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2867-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

et al. 2016

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“…The anti-miR-223-treated mice showed the amelioration of score and incidence of arthritis, histopathologic examination, as well as the attenuation of osteoclastogenesis and bone erosion in joints [91]. In clinical trials, miR-122-targeted therapy in chronic hepatitis C patients has been reported to be long-term safe and effective [92,93]. Furthermore, miRNA-masking (miR-mask) technology is another sort of antisense oligonucleotides approaches.…”

Section: Micrornas and Lncrnas-targeting Therapeuticsmentioning

confidence: 95%

Epigenetics in autoimmune diseases: Pathogenesis and prospects for therapy

Zhang

2015

Autoimmunity Reviews

100

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“…miRNA injection may be a promising therapeutic approach in future for SSc treatment, but this aim is not beyond the realm of possibility which is supported by the successful and well-tolerated use of miRNAs in rodents as well as in non-human primates. Most strikingly, a report suggests that local delivery of anti-miRNAs, such as intradermal application, may be an alternative therapeutic strategy, and the first human clinical trial has been performed to investigate the effects of anti-miR-122 delivery in patients with hepatitis C [96,97]. However, the first human clinical trial of anti-miRNAs in SSc has not been performed, thus new discovery of miRNAs is needed in future to guide the further animal experiments and clinical trials.…”

Section: Conclusion and Prospectivementioning

confidence: 98%

Critical roles of microRNAs in the pathogenesis of systemic sclerosis: New advances, challenges and potential directions

Miao,

Xiong,

et al. 2015

International Immunopharmacology

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Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients

Cited by 163 publications

References 33 publications

In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

Epigenetics in autoimmune diseases: Pathogenesis and prospects for therapy

Critical roles of microRNAs in the pathogenesis of systemic sclerosis: New advances, challenges and potential directions

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