A non-viral nanoparticle gene therapy delivery platform for treating Cystic Fibrosis and other diseases

SUMMARY The use of gene therapy for chronic lung diseases, such as cystic fibrosis, has increased dramatically since the early 2000s, but a safe, long-term delivery method remains missing. Despite a highly safe profile with partial therapeutic effects after successful delivery in CF patients, the gene transfer efficiency, in terms of transfection per particle, remains limited when using viral-based delivery systems. Genexys has developed a modular non- viral gene transfer platform that directly addresses the limitations of current CF gene therapeutic strategies. The technology is a DNA and RNA nanoparticle platform capable of holding large genes combined with uptake enhancers that inhibit proteins that limit gene transfer to targeted cells. Our foundational work has demonstrated our DNA nanoparticle technology successfully delivers therapeutic loads of the cystic fibrosis transmembrane conductance regulator (CFTR) in cell culture, animal models, and human subjects. Our unique proprietary enhancer library allows our non-viral system to overcome the gene transfer limitations of our competitors. This library of enhancer molecules is hypothesize to work through Nucleolin (NCL), an essential protein for DNP- based cell surface receptor that facilitates gene membrane transfer and nuclear trafficking. This project further develops our non-viral nanoparticle gene therapy system in an in vitro and in vivo context. We aim to demonstrate transgene delivery with enhancers restores primary function in human bronchial epithelia cells and can overcome muscus inhibition in mouse FDA IND-enabling studies. We will also explore different delivery formulations. The deliverables will include an established efficacy of this product in a commercially available gene therapeutic, and that this revolutionary technology can be available to all CF patients needing advance treatment options.