In Vitro and In Vivo Efficacy of SYL040012, a Novel siRNA Compound for Treatment of Glaucoma

Martínez, Tamara; González, Marı́a Victoria; Roehl, Ingo; Wright, Natalia; Pañeda, Covadonga; Jiménez, Ana I.

doi:10.1038/mt.2013.216

Cited by 94 publications

(66 citation statements)

References 43 publications

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“…Additionally, the delivery of siRNAs in vivo into tumors was 10-and 30-fold more effective than that using cationic liposomes and naked siRNAs, respectively (Landen et al, 2005;Halder et al, 2006). Moreover, locally delivered siRNA has also been successfully used in the eyes, respiratory system, and pancreatic cancer (Zamora et al, 2011;Zorde Khvalevsky et al, 2013;Martínez et al, 2014), suggesting further potential for MRP4 siRNA.…”

Section: The Potential Of Mrp4 As a Drug Targetmentioning

confidence: 98%

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

Wen

Luo

Huang

et al. 2015

J Pharmacol Exp Ther

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Multidrug-resistant protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is distributed in a variety of tissues and a number of cancers. As a drug transporter, MRP4 is responsible for the pharmacokinetics and pharmacodynamics of numerous drugs, especially antiviral drugs, antitumor drugs, and diuretics. In this regard, the functional role of MRP4 is affected by a number of factors, such as genetic mutations; tissue-specific transcriptional regulations; post-transcriptional regulations, including miRNAs and membrane internalization; and substrate competition. Unlike other C family members, MRP4 is in a pivotal position to transport cellular signaling molecules, through which it is tightly connected to the living activity and physiologic processes of cells and bodies. In the context of several cancers in which MRP4 is overexpressed, MRP4 inhibition shows striking effects against cancer progression and drug resistance. In this review, we describe the role of MRP4 more specifically in both healthy conditions and disease states, with an emphasis on its potential as a drug target.

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Section: The Potential Of Mrp4 As a Drug Targetmentioning

confidence: 98%

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

Wen

Luo

Huang

et al. 2015

J Pharmacol Exp Ther

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“…SYL040012 (bamosiran, by Sylentis, S.A.), targeting β2-adrenergic receptor, was shown to decrease intraocular pressure in normotensive and hypertensive animal models [88]. In a phase I trial initiated in 2009, SYL040012 eye drops was reported to be safe and well-tolerated.…”

Section: Clinical Experience With Sirna-based Therapeuticsmentioning

confidence: 99%

Preclinical and clinical development of siRNA-based therapeutics

Özcan

Özpolat

Coleman

et al. 2015

Advanced Drug Delivery Reviews

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301

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Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment.

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“…siRNA is also pursued for glaucoma therapy. siRNA targeting β 2 -adrenoceptors (SYL040012) was shown to reduce the expression of β2 adrenergic receptor and the production of aqueous humor, thereby reducing intraocular pressure [19]. …”

Section: Therapeutic Applications Of Sirna and Target Genesmentioning

confidence: 99%

Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines

Park

Pei

et al. 2016

Advanced Drug Delivery Reviews

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Small interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bioconjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. However, most cases address local applications or diseases in the filtering organs, reflecting remaining challenges in systemic delivery of siRNA. The difficulty in siRNA delivery is in large part due to poor circulation stability and unfavorable pharmacokinetics and biodistribution profiles of siRNA. This review describes the pharmacokinetics and biodistribution of siRNA nanomedicines, focusing on those reported in the past 5 years, and their pharmacological effects in selected disease models such as hepatocellular carcinoma, liver infections, and respiratory diseases. The examples discussed here will provide an insight into the current status of the art and unmet needs in siRNA delivery.

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In Vitro and In Vivo Efficacy of SYL040012, a Novel siRNA Compound for Treatment of Glaucoma

Cited by 94 publications

References 43 publications

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

Preclinical and clinical development of siRNA-based therapeutics

Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines

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