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New, natural DNA-based drugs are safe, potent activators of immune system

Mary Ann Liebert, Inc./Genetic Engineering News

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IMAGE: Nucleic Acid Therapeutics is an authoritative peer-reviewed journal published bimonthly in print and online that focuses on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related... view more

Credit: ©Mary Ann Liebert, Inc., publishers

New Rochelle, NY, April 7, 2015--An experimental single-stranded oligonucleotide-based drug, MGN1703, comprised only of natural DNA components, stimulates the human immune system to fight infections and attack cancer cells without causing the harmful side effects associated with similar compounds that also contain non-natural DNA components. The design and structural characteristics of MGN1703, which is in clinical testing to treat a variety of cancers, affect its potency and toxicity, as described in an article in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers . The article is available free on the Nucleic Acid Therapeutics website until April 24th, 2015.

"Design and Structural Requirements of the Potent and Safe TLR-9 Agonistic Immunomodulator MGN1703" presents a detailed look at this DNA molecule, which contains non-methylated cytosine nucleotides in cytosine-guanine pairs, a signature often found in bacteria and viruses that sends a danger signal to human immune cells. These compounds bind to and activate toll-like receptor 9 (TLR9), triggering a cascade of signaling pathways in the immune system that enable recognition and destruction of foreign cells.

Manuel Schmidt and Matthias Schroff, Mologen AG (Berlin, Germany), Nicole Hagner and Burghardt Wittig, Freie Universitaet Berlin, Alberto Marco, Universidad Autonoma de Barcelona (Spain), and Sven König-Merediz, Vivotecnia (Madrid, Spain) describe their approach to the molecular design of MGN1703. They avoided the need to incorporate non-natural components into the DNA backbone to enhance its potency and stability by instead manipulating its size and shape.

"Moving forward to solve the concerns and disappointment of clinical implementation of cytosine-phosphodiester-guanine oligodeoxynucleotides, this work is an important step towards the application of a new class of safe and efficacious immunomodulators in humans," says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.

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About the Journal

Nucleic Acid Therapeutics is an authoritative peer-reviewed journal published bimonthly in print and online that focuses on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. The Journal is under the editorial leadership of Editor-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC, and Executive Editor Graham C. Parker, PhD. Nucleic Acid Therapeutics is the official journal of the Oligonucleotide Therapeutics Society. Complete tables of content and a sample issue may be viewed on the Nucleic Acid Therapeutics website.

About the Society

The Oligonucleotide Therapeutics Society is an open, non-profit forum to foster academia- and industry-based research and development of oligonucleotide therapeutics. The society brings together the expertise from different angles of oligonucleotide research to create synergies and to bring the field of oligonucleotides to its full therapeutic potential.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Human Gene Therapy, ASSAY and Drug Development Technologies, Applied In Vitro Toxicology, and DNA and Cell Biology. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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