Overview
Chronic inflammation is a hallmark of a number of age-related diseases, as well as of aging itself. Nuclear element-1 (L1) plays a key role in this inflammatory process. We have developed the first inhibitors of the L-1 endonuclease (EN) domain and the first of any retrotransposon-encoded EN. Our technology sheds light on the regulators that control age-related inflammation, on the causal relationship of these regulators to chronic degenerative diseases, and on potential methods for preventing and reducing age-associated inflammation.
Market Opportunity
One hallmark of aging is the accumulation of senescent cells that contribute to sterile inflammation, which underlies many age-associated diseases, including heart disease cancer, diabetes, and Alzheimer's disease, as well as aging itself. Indeed, many inflammatory markers are significant predictors of mortality. L1, which represents approximately 17% of the human genome, plays a key role in this inflammatory process. An L1 inhibitor could provide an effective way to prevent these diseases.
Innovation and Meaningful Advantages
We have developed the first inhibitors of the L-1 EN domain and the first of any retrotransposon-encoded EN. We have also defined biochemical, structural, and cell-culture approaches to further characterize these inhibitors, as well as other candidate compounds. Our inhibitors have been shown to be effective both in vitro and in cells. Our technology sheds light on the regulators that control age-related inflammation, on the causal relationship of these regulators to chronic degenerative diseases, and on potential methods for preventing and reducing age-associated inflammation.
We have developed two new assays to quantify the impact of both existing and new L1 EN inhibitors on L1 activity. In addition, we investigated the effects of L1 EN inhibitors on L1-induced DNA damage in HeLa cells and have demonstrated that several inhibitors reduce DNA damage, compared with no inhibitor treatment.
Collaboration Opportunity
We are interested in exploring 1) research collaborations with leading pharmaceutical companies; and 2) licensing opportunities with pharmaceutical companies.
Principal Investigator
John Sedivy, PhD
Hermon C. Bumpus Professor of Biology
Associate Dean and Director, Center for the Biology of Aging
Brown University
IP Information
US Provisional Application 63/387,188 Filed December 13, 2022
Publications
D’Ordine AM, Jog G, Sedivy JM. Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease. bioRxiv preprint 2022 Dec. 29. doi.org/10.1101/2022.12.29.522256.
Contact
Andrew Bond, PhD
Senior Director of Business Development
andrew_bond@brown.edu
Brown Tech ID 3287