Synthetic Biology Approaches in Immunology

Abstract

Breakthroughs in gene synthesis has allowed synthetic biologists the ability to design any DNA sequence of interest, enabling the possibility to create complex systems inside cells with novel functions to tackle problems in immunology. Synthetic immunology of mammalian cells expressing natural or synthetic genes can guide and induce immune responses in patients. Through recent developments in engineering chimeric receptors, it is now feasible to customize control over engineered cells to target the disease sites with specificity. These cells can avoid immune rejection if derived from expandable cell types (e.g., stem cells or T cells) and then can be grown in abundance before implantation. However, safety concerns of engineered cells in circulation necessitates the development of a wide range of mechanisms to kill cells after their therapeutic life ends. This therapeutic effect is still predominantly the secretion of therapeutic proteins, but novel therapeutic interventions have been explored by synthetic biologists. In the pursuit of engineering new cell functions for synthetic immunology, it is possible that many problems previously thought intractable may actually be possible.

Synthetic Biology Meets Ca2+ Release-Activated Ca2+ Channel-Dependent Immunomodulation

“…Synthetic biology comprises methods and tools that are used to manipulate basic biological components at the level of DNA, proteins, cells, or even multicellular structures in order to redesign a biological process [ 207 , 208 , 209 ]. An elegant method of rewiring biological processes is the control of physical distance, which is beneficial for various processes in nature, including cell–cell contacts, signal transduction, and protein transport.…”

“…Researchers have taken advantage of this fact to better understand cellular signaling processes using small molecules [ 210 ], proteases [ 211 ], or photosensory modules [ 212 ] to induce the proximity of cellular components. Furthermore, in synthetic immunology, engineered chimeric receptors have made it possible to selectively target disease [ 208 ]. Arguably, the greatest advantage of induced proximity is the potential to rapidly initiate a downstream signaling process in living cells and monitor its consequences, which enables precise kinetic studies [ 210 , 213 ].…”

“…Kill switches offer a new possibility for cell killing, but these are difficult to maintain in the genome due to natural selection. Although engineered immune cells have reached the level of clinical trials, significant research work still needs to be performed in this area to create safe systems for their therapeutic use [ 208 ].…”