New method described for quantifying antisense oligonucleotides in nuclei
Credit: Mary Ann Liebert, Inc., publishers
New Rochelle, NY, November 14, 2019–A novel method uses subcellular fractionation to quantify label-free antisense oligonucleotides (AONs)- designed to silence targeted genes – that have crossed into the nucleus of a cell, where they can exert their effects. Researchers used this method to correlate nuclear entry of several AON molecules with target gene knockdown and they report their results in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. Click here to read the full-text open access article for free on the Nucleic Acid Therapeutics website.
Troels Koch and colleagues from Roche Innovation Center Copenhagen, Hørsholm, Denmark coauthored the article entitled “Nuclear and Cytoplasmatic Quantification of Unconjugated, Label-Free Locked Nucleic Acid Oligonucleotides.” Their method combines three main techniques: subcellular fractionation; nucleus counting; and Locked Nucleic Acid (LNA) sandwich Enzyme-Linked Immunosorbent Assay (ELISA) to determine the absolute numbers of AONs in nuclei. These unconjugated LNA oligonucleotides lack any labels that could alter their distribution in the cell. The researchers showed that increased nuclear entry was proportional to increased target gene knockdown, but depending on the compound and the target, other factors could impact the target transcript level reduction.
“As we anticipate the increase in oligonucleotide-based therapeutics, we must acknowledge it is one thing to know how many oligonucleotides are administered to the patient, it is quite another to know how many accumulate in the target cell nuclear fraction,” 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.
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 Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center and Annemieke Aartsma-Rus, PhD, Leiden University Medical Center, 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, GEN (Genetic Engineering & Biotechnology News), 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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