Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder caused by pathogenic variants in ATP-binding cassette subfamily C, member 6 (ABCC6). ABCC6 typically exports ATP, which is then converted by ENPP1 into AMP and pyrophosphate (PPi). Because PPi is a potent inhibitor of calcification, reduced systemic PPi production is a key driver of PXE. University of Pennsylvania investigators and collaborators proposed applying liver-targeted variant correction via genome editing as a single-intervention therapeutic approach for PXE, leading to subsequent restoration of systemic PPi.

Opioid use disorder (OUD) remains a significant public health crisis, with over 5 million people diagnosed in the U.S. in 2023 and more than 80,000 fatal overdoses involving opioids each year. Current FDA-approved medications for OUD target the micro-opioid receptor, but these treatments are still associated with high relapse rates during abstinence.