The emerging era of cell engineering: Harnessing the modularity of cells to program complex biological function

Abstract

A new era of biological engineering is emerging in which living cells are used as building blocks to address therapeutic challenges. These efforts are distinct from traditional molecular engineering—their focus is not on optimizing individual genes and proteins as therapeutics, but rather on using molecular components as modules to reprogram how cells make decisions and communicate to achieve higher-order physiological functions in vivo. This cell-centric approach is enabled by a growing tool kit of components that can synthetically control core cell-level functional outputs, such as where in the body a cell should go, what other cells it should interact with, and what messages it should transmit or receive. The power of cell engineering has been clinically validated by the development of immune cells designed to kill cancer. This same tool kit for rewiring cell connectivity is beginning to be used to engineer cell therapies for a host of other diseases and to program the self-organization of tissues and organs. By forcing the conceptual distillation of complex biological functions into a finite set of instructions that operate at the cell level, these efforts also shed light on the fundamental hierarchical logic that links molecular components to higher-order physiological function.