This project establishes a non-viral ultrasound-mediated sonoporation platform for delivering rolling circle-amplified DNA constructs to the liver, inducing antigen-specific immune tolerance for conditions like T1D and MS. The approach uses clinical ultrasound systems and FDA-approved microbubbles to achieve targeted and repeatable gene delivery. Ultimately, the HepGene project aims to enable durable, site-specific immune modulation, with broad applications in autoimmunity and gene therapy redosing.