We have been working in the area of RNA delivery for more than a decade, using a range of disease model systems, including viruses and viral-caused cancer, to demonstrate in vivo efficacy. We recently licenced our SARS-CoV-2 siRNA technology to industry. Indeed, encapsulation of siRNAs in our novel LNPs, followed by in vivo injection, clears SARS-CoV-2 infection in the lungs and allows complete survival in treated mice. For this work we simultaneously developed and screened two novel lipid nanoparticle formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. However, while lipid nanoparticles (LNPs) are a clinical reality, current versions have several deficiencies. They only deliver 1% of their payload to the cytoplasm, they don’t distribute to important tissues where clinical interventions are needed (e.g. the brain), and their use of phagocytic inhibitors like PEG elicit inflammatory immune reactions. To address this, we will present data on the next generation of LNPs that will overcome these issues. We will show a range of disease models from cancer to COVID, Hendravirus, and RSV. We will show strategies to deliver to different organs such as the lungs and brain. Overall, the next generation of LNPs will vastly improve upon today’s generation 1 versions.