Toward computer guided design of cells for therapeutics and beyond by Hersh Bhargava

Hersh Bhargava

UC San Francisco | NVIDIA

Reprogramming cells with therapeutic functions is a promising strategy for transcending conventional molecular therapeutics. However, current approaches for figuring out how to reprogram cells are based on slow and expensive ad hoc iteration in the lab. I am developing computational strategies based on multiscale mathematical models for executing computer-guided cell design.

ABSTRACT

Living cells have tremendous potential to be reprogrammed for use as next-generation, intelligent therapeutic agents. The promise of such designer cells has been underscored by the recent clinical success of CAR-T cells, which have cured hematological cancers in some cases. By leveraging systems and synthetic biology approaches, it is proving possible to engineer complex programs into human cell scaffolds. Spatially targeted payload delivery, establishment of tissue residence, and chemical microenvironment modulation are exciting possibilities of cell design. To reliably reprogram human cell scaffolds with such next-generation capabilities, it is essential to develop principled design strategies that are augmented with computational methods. Such strategies would enable in silico profiling of many possible biochemical strategies for achieving a therapeutic capability of interest, which is critical for designing complex circuitry where trial and error or ad hoc design strategies are unfeasible. I am developing strategies for computationally augmented cell design, with the goal of creating synergy between rapid in silico iteration and strategic in vitro and in vivo validation. I hypothesize that this approach will improve the cell design workflow as well as the sophistication of the capabilities of designer cells.

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