Our research seeks to create function through synthesis-informed design, often inspired by natural products and directed at unsolved medical problems. This lecture will focus on the as yet unachieved goal of eradicating HIV/AIDS, first-in-kind strategies for treating Alzheimer’s disease and the use of our own cells to make agents that elicit an immune response to prevent or cure cancer. These seemingly disparate function-oriented synthesis studies (<i>Accts.</i> 2015) are based on a unifying strategy involving the use of small molecules or mRNA delivery to induce protein expression. For an HIV/AIDS cure, prostratin, bryostatin and their analogs are used to induce cell activation, protein expression and thus clearance of reservoir cells that harbour the HIV virus, thereby eliminating the source of chronic HIV reinfection which with current antiretroviral therapy would lead to a cure. We have now reported and will update in this lecture clinical supply impacting syntheses of prostratin (Science 2008), bryostatin (Science 2018) and their analogs (e.g. ACS Central Sci. 2018) as well as their activities  (e.g., PLoS Pathogens 2017, Virology 2018). Bryostatin is also in a phase II clinical trial for Alzheimer’s disease. Significantly it is also proposed for clinical evaluation as a platform technology to enhance CAR-T cell cancer immunotherapy targeting CD22. We also devised an alternative approach to protein induction based on the use of a new drug delivery platform (CARTs: PNAS 2017, 2018, 2018) that enables delivery of mRNA into cells and thus control of protein expression. As will be presented in this lecture, we have found that this CART-RNA technology can be organ targeted and can be used to prevent or cure cancer in mice.   <br/>

Therapeutic function through synthesis-informed design: Approaches to HIV/AIDS eradication, Alzheimer's disease, and enhanced cancer immuno-therapy

2019 Spring National Meeting

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