Value Proposition
路 Autoantibody that promotes DNA degradation to diminish inflammation
路 Enhances endonuclease DNase1L3 activity
路 Avoids kidney-mediated inflammatory response
Unmet Need
路 Extracellular DNA, also called cell-free DNA, released from dying cells or activated immune cells can be recognized by the immune system as a danger signal causing or enhancing inflammation. The cleavage of extracellular DNA is crucial for limiting the inflammatory response and maintaining homeostasis. The pathogenesis of a significant number of diseases has been linked to the abnormal accumulation of extracellular DNA, such as systemic lupus erythematosus (SLE), cystic fibrosis, asthma, cancer, Alzheimer disease, sepsis, acute kidney injury, acute liver injury, ischemic reperfusion syndrome, empyema thoracis, and thrombosis (Laukova). Currently, there are a limited number of medications and therapies approved for these purposes. Thus, there is a need for new treatment strategies to improve the clearance of cell-free DNA and high morbidity and mortality associated with these diseases.
Technology Description
路 Researchers at Johns Hopkins have identified an antibody that targets cell-free DNA which can mediate inflammation that helps treat diseases associated with abnormal accumulation of extracellular DNA. The discovery is an anti-dsDNA autoantibody, which have variety of functions and binding targets, specific to the body鈥檚 own dsDNA. Under physiological conditions, the anti-dsDNA autoantibody binds to double stranded DNA and associates with endonuclease DNase1L3 to perform its DNA degradation functions. Furthermore, this antibody is a non-nephritogenic agent, which prevents the kidney鈥檚 inflammatory response, whereas other anti-dsDNA antibodies have been shown to induce nephritis within the kidney, especially in the context of SLE.
Stage of Development
路 In vitro assays to assess DNA degradation abilities have been conducted and published. Researchers are now seeking to conduct in vivo studies to define the antibody鈥檚 DNA degradation mechanisms in a human disease model.
Data Availability
路 Data available at publication below.
Publication
路 https://doi.org/10.1038/s41467-023-37083-x
