Share this article WASHINGTON, March 16, 2021 /PRNewswire/ -- An article published in Experimental Biology and Medicine (Volume 246, Issue 6, March, 2021) reports a new nucleic acid-based approach for therapeutics targeting inflammation. The study, led by Dr. Anthony Bell Jr, in the Department of Chemistry and Biochemistry at the University of San Diego in San Diego, CA (USA), reports four novel cruciform DNA ligands that exhibit increased nuclease-resistance, thermostability, and target-binding affinity. HMGB1 (High Mobility Group B1) is an important molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. HMGB1 plays two different but critical roles inside and outside of cells. Inside cells, HMGB1 bends DNA into arrangements or scaffolds that facilitate gene expression. Outside cells, HMGB1 functions as a proinflammatory cytokine that can be either a "friend" or "foe" and initiate cytokine reactions that ward off harmful stimuli or worsen autoimmune dysfunction. Previous work has shown that nucleic acids directed against HMGB1 can be used to block HMGB1 function. Nonetheless, the clinical use of nucleic therapeutics is hampered by their thermal instability, short half-life due to degradation by endogenous nucleases, and low binding affinity for their target.