Developing an Anti-FZD7 scFv for Lipid Nanoparticle based Drug Delivery

The WNT signaling pathway plays an important role in embryonic development and adult tissue homeostasis. However, cancer cells often can use this pathway to acquire ‘stem-cell like’ properties aiding proliferation, self-renewal and chemoresistance[1]. Several therapies targeting the WNT pathway have been developed successfully, but owing to adverse side-effects, many of these have not advanced through clinical trials[1]. Further, the WNT pathway’s pleiotropic nature and complexity across different cancer types, necessitates the development of precise and targeted therapies. Previous studies have found that the WNT receptor, Frizzled class receptor 7 (FZD7), shows elevated expression in several cancer types, making it a potential target for cancer therapies[4]. Lipid nanoparticles (LNPs) have been used in targeted cancer therapies for the diversity of payloads they can accommodate and their enhanced permeability and retention in tumor vasculature[16]. Thus, I propose that LNP enclosed anti-cancer payloads can be specifically delivered to FZD7 expressing tumor cells with the help of a targeting molecule. To that end, I have engineered a FZD7 targeting Single Chain Variable Fragment (F7-scFv) and tested lipid nanoparticles conjugated with the F7-scFv for their ability to bind to cells in a receptor dependent manner, to potentially be used to deliver anticancer therapeutics to tumors