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Can Toxicity of a DNA Drug Be Predicted and Minimized?
New Rochelle, NY, August 26, 2013—New classes of therapeutic antisense oligonucleotides can have toxic effects on the liver. A novel machine learning-based approach used to predict the hepatotoxic potential of an antisense drug based on its chemical sequence is presented in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. The article is available on the Nucleic Acid Therapeutics website.
Peter Hagedorn and coauthors from Santaris Pharma, Hørsholm, Denmark, and University of Copenhagen, Denmark, describe the use of machine learning techniques to develop a method of classifying therapeutic oligonucleotides based on their DNA sequence and modification patterns. Computers create a classification scheme linking this variation to a compound's potential to cause liver toxicity.
In the article "Hepatotoxic Potential of Therapeutic Oligonucleotides Can Be Predicted from Their Sequence and Modification Pattern," the authors demonstrate the use of this approach to predict the hepatotoxicity of a validation set of oligonucleotides with 74% accuracy. They also use the classifier scheme to identify a therapeutic oligonucleotide with high potential liver toxicity and show how the drug could be redesigned to reduce its potential toxicity.
“As is true of all potential therapeutic entities, whether small molecules or nucleic acid-based drugs, it is critical to understand as much as possible about possible toxic effects before proceeding to clinical trials," says Executive Editor Fintan Steele, PhD, SomaLogic, Inc., Boulder, CO. “The approach described by these authors holds great promise for maximizing the safety of in vivo testing and, we hope, the eventual clinical use of these new antisense-based compounds.”
Nucleic Acid Therapeutics is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC, and C.A. Stein, MD, PhD, City of Hope National Medical Center, Duarte, CA; and Executive Editor Fintan Steele, PhD (SomaLogic, Boulder, CO).
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. Nucleic Acid Therapeutics is the official journal of the Oligonucleotide Therapeutics Society. Complete tables of content and a free sample issue may be viewed on the Nucleic Acid Therapeutics website.
About the Society
The Oligonucleotide Therapeutics Society is an open, nonprofit 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 promising areas of science and biomedical research, including Human Gene Therapy, Human Gene Therapy Methods, Human Gene Therapy Clinical Development, ASSAY and Drug Development Technologies, 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.