CINCINNATI, March 28, 2012 /PRNewswire-USNewswire/ — Researchers have taken a critical step in understanding how allergic reactions occur after identifying a genetic signature for regulation of a key immune hormone, interleukin (IL-13).
Scientists from Cincinnati Children’s Hospital Medical Center say the finding opens the potential for new molecular targets to treat allergic disease. They report on March 28 in Mucosal Immunology that a particular microRNA, miR-375, is regulated by IL-13, and in turns regulates how IL-13 induces pro-allergic changes, particularly in epithelial cells in the lung and esophagus.
The data support a role for miR-375 in asthma and in eosinophilic esophagitis (EoE), a severe, often painful food allergy that renders children unable to eat a wide variety of foods. EoE can also cause weight loss, vomiting, heartburn and swallowing difficulties.
“The identification of a microRNA that regulates IL-13-induced changes and inflammatory pathways is a significant advancement for the understanding and future treatment of allergic disease,” says Marc E. Rothenberg, MD, senior investigator on the study and director of the Division of Allergy and Immunology and Center for Eosinophilic Disorders at Cincinnati Children’s. “MiR-375 is proof of principle that microRNAs are involved in fine-tuning IL-13-mediated responses, which opens up a set of new possibilities for novel therapeutic targets for treatment of allergic disease.”
IL-13 induces changes in epithelial gene and protein expression that are important in the onset of many allergic diseases, including EoE. Notably, expression of miR-375 was consistently [click to continue…]
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-New study published in Science Translational Medicine demonstrates microRNA-21 contributes to fibrogenesis in the kidney
-Regulus, in partnership with Sanofi, developing novel anti-fibrotic therapies targeting microRNAs
B.N. Chau et al.
“MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways”
Sci Transl Med 15 February 2012:
Vol. 4, Issue 121, p. 121ra18
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003205
http://stm.sciencemag.org/content/4/121/121ra18
LA JOLLA, Calif., Feb. 16, 2012 /PRNewswire/ — Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced that new preclinical data investigating the role of microRNA-21 (miR-21) in the treatment of kidney fibrosis has been published in the journal Science Translational Medicine. Regulus’ lead program for fibrosis targets miR-21, which is up-regulated in fibrotic tissues of humans. Previous preclinical studies by Regulus scientists and collaborators have shown that therapeutic oligonucleotides targeting miR-21 (anti-miR-21) can decrease fibrosis in preclinical models by reducing the expression of extracellular matrix proteins. Despite the current burden of fibrosis-related human disease, there are few therapies that can specifically treat this devastating disease.
“We are pleased with the published results demonstrating that targeting miR-21 with proprietary anti-miR oligonucleotides is effective at preventing kidney fibrosis in preclinical models,” said Neil W. Gibson, Ph.D., Regulus’ Chief Scientific Officer. ”We plan to select an anti-miR-21 development candidate [click to continue…]
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Patent Protects Use of UNAs in Multiple Nucleic Acid Constructs Including siRNAs, microRNA Mimics, Antagomirs and Single-Stranded Constructs
BOTHELL, WA–(Marketwire – Jan 23, 2012) – Marina Biotech, Inc. (NASDAQ: MRNAD), a leading oligonucleotide-based drug discovery and development company today announced that the Intellectual Property Office of New Zealand (IPONZ) has issued a Notice of Acceptance for patent application 580712. The claims broadly cover multiple sequence independent and length independent, nucleic acid constructs having one or more unlocked nucleobase analogs (UNAs). The nucleic acid constructs of the patent include both RISC and dicer length siRNAs, both microRNA mimetics and microRNA antagomirs as well as single-stranded oligonucleotides.
“The company continues to deliver on a patent strategy which expands and protects our broad oligonucleotide therapeutics platform,” stated J. Michael French, President and CEO at Marina Biotech. “This allowed patent is part of our global UNA patent portfolio providing broad and comprehensive protection for multiple, distinct UNA containing nucleic acid constructs all of which can modulate gene expression through distinct cellular mechanisms including RNAi, mRNA translational inhibition, steric blocking or microRNA pathways. This patent allowance reinforces our belief that we will continue to obtain patent protection for our UNA technology in other countries thereby strengthening the company’s intellectual property position for our broad oligonucleotide drug discovery platform.”
UNA are non-nucleotide, acyclic monomers which provide greater structural flexibility in a nucleic acid strand. Their value has been demonstrated in Marina Biotech’s proprietary UsiRNA constructs which are double-stranded small interfering RNA (siRNA) incorporating at least one UNA monomer and are distinct from the standard siRNA constructs used by others in the industry. UsiRNAs are specifically designed to provide greater specificity for RNAi-based therapeutics. Substitution with UNA [click to continue…]
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LONDON, January 9, 2012/PRNewswire-FirstCall/ –
- Third collaboration to investigate the potential application of Silence’s proprietary RNAi delivery technologies in the development of novel microRNA-based therapeutics
Silence Therapeutics plc (AIM: SLN) (“Silence”), a leading RNA interference (RNAi) therapeutics company, announces that it has signed an agreement with miRagen Therapeutics, Inc. (“miRagen”), to assess the delivery potential of Silence’s proprietary DBTC delivery system with miRagen’s novel microRNA- (miRNA-) based therapeutics. MiRagen is a pre-clinical stage biopharmaceutical company founded to develop innovative miRNA-based therapeutics for the treatment of cardiovascular and muscle disease.
Under the terms of the agreement, miRagen will provide Silence with specific miRNA sequences, which Silence will formulate with its proprietary DBTC delivery system in order to develop multiple candidate drugs. MiRagen will undertake in vitro and in vivo studies of the candidate drugs developed under the agreement and select lead candidates for further evaluation. Financial terms of the collaboration are not disclosed.
DBTC is a proprietary RNAi delivery system developed by Silence. It is a novel lipid-based formulation that functionally delivers short interfering RNA (siRNA) to liver endothelial cells, hepatocytes and other liver cell types with high efficiency.
Thomas Christely, Chief Executive Officer of Silence Therapeutics, said: “We are delighted to be collaborating with miRagen. This is the third collaboration that [click to continue…]
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Collaboration to investigate potential application of Silence’s novel AtuPLEX(TM)and DBTC delivery technologies in the development of novel microRNA therapeutics targeting cancer
LONDON, October 24, 2011/PRNewswire-FirstCall/ –
Silence Therapeutics plc (AIM: SLN) (“Silence”), a leading RNA interference (RNAi) therapeutics company, today announced that it has entered into an agreement with Mirna Therapeutics Inc. (“Mirna”), a biopharmaceutical company pioneering microRNA-based therapeutics for cancer, to assess the delivery capabilities of Silence’s proprietary AtuPLEX(TM) and DBTC delivery systems for Mirna’s novel microRNAs.
Under the terms of the agreement, Mirna will provide Silence with specific miRNA sequences, which Silence will formulate with its AtuPLEX(TM) and DBTC delivery systems in order to develop multiple candidate drugs. Mirna will undertake in vitro and in vivo studies of the candidate drugs developed under the agreement and select lead candidates for further evaluation. Financial terms of the deal were not disclosed.
Thomas Christely, Chief Executive Officer of Silence Therapeutics, said: “We are delighted to be collaborating with Mirna. This is our second collaboration exploring the use of Silence’s delivery technologies to deliver microRNAs. However, it is [click to continue…]
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