Antisense molecules: A new class of drugs Daniel P. Potaczek, MD, PhD, Holger Garn, PhD, Sebastian D. Unger, Harald Renz, MD  Journal of Allergy and Clinical Immunology  Volume 137, Issue 5, Pages 1334-1346 (May 2016) DOI: 10.1016/j.jaci.2015.12.1344 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Mode of action of antisense molecules as inhibitors of disease-associated protein expression. A, Under healthy conditions, cells permanently generate a variety of proteins needed for their own homeostasis and interaction with their environment in a tightly controlled process. Gene-specific mRNAs are transcribed from the respective DNA regions in the nucleus (1), and mRNAs are transferred to the cytoplasm (2). At the ribosomes, mRNA information is translated into the corresponding protein sequence (3). After appropriate processing, proteins are transported to their final location, which might be intracellular, membrane bound, or secreted to the extracellular space (4). B, Following disease-associated signals, the steady state of cells becomes disturbed, and transcription/translation of a variety of (disease-associated) genes/proteins can be significantly increased. This leads to a dysregulated cellular response, which drives the pathological process. C, Highly gene-specific antisense molecules can bind and subsequently block or even cleave targeted disease-associated mRNA molecules. This interaction inhibits translation into the respective protein and rebalances cellular activities toward normal conditions. Journal of Allergy and Clinical Immunology 2016 137, 1334-1346DOI: (10.1016/j.jaci.2015.12.1344) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Strategy of the systematic literature search and its results. Journal of Allergy and Clinical Immunology 2016 137, 1334-1346DOI: (10.1016/j.jaci.2015.12.1344) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions