Only 12% of drugs entering clinical trials are ultimately approved for patient use by regulatory agencies such as the U.S. Food and Drug Administration (FDA), taking ~12-15 years from discovery to market commercialization. This inefficient process is partly attributed to the use of animal models as the gold standard for preclinical drug testing; however, these models are not only expensive and time-consuming but also raise ethical concerns and often fail to accurately predict human responses due to significant cross-species physiological differences. As a result, the USA FDA Modernization Act 2.0 encourages the development of novel methodologies, such as advanced in vitro assays, microphysiological systems, and organoids as humanized platforms for preclinical studies. We are utilizing synthetic biology tools to engineer mammalian cells to form tissues that capture solid tumors and cartilage. These environments will enable the study of drug transport, drug delivery, and therapeutic screening.
Engineered cells for cell therapy
Advancements in engineered immune cell therapy, such as CAR T-cell therapy for treating blood cancer, have opened promising avenues for genetically engineering immune cells and stem cells for therapeutic applications. In particular, engineering human-induced pluripotent stem cells (hiPSCs) derived from a patient’s somatic cells enables autologous cell therapy, thereby reducing the risks of immune rejection. To that end, we are engineering hiPSCs using gene regulatory networks to achieve precise differentiation into various cell types while ensuring their safe and tissue-specific delivery for cancer immunotherapy. Additionally, the differentiated cells will be utilized to engineer multicellular living systems for tissue regeneration applications.
Therapeutics must overcome various biological barriers to accumulate at the disease site in a clinically relevant dose to be effective. Drug delivery vehicles need to be designed to interact favorably with the biological microenvironment, enabling them to penetrate these biological barriers and remain at the disease site until the desired therapeutic outcome is achieved. To facilitate this, we will develop combinatorial screening strategies, such as phage display, to identify biological moieties that can be surface-functionalized for tissue-specific delivery of various drug delivery vehicles.