Drug Discovery

Synthetic cells

  • A typical synthetic cell is composed of the following three elements: Inducer, genetic circuits and an output signal.

  • An inducer could be small molecules, a ligand (molecule which binds to the receptor) of a membrane receptor or even light. (Figure 1A)

  • Inducer triggers a de novo-designed genetic circuit (Figure 1B).

  • Inducing this circuit produces an output signal that can be followed by a light-emitting reporter gene (GFP)(Figure 1C).

  • These three basic constituents can be integrated in different manners according to the type of applications in drug discovery.

Immunotherapy

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system.

Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.

Immunotherapy is used to induce immune response. Chimeric Antigen Receptor T-cell therapy (CAR) is a method of immunotherapy which is a growing practice in the treatment of cancer.

T cells are a part of the immune system that focuses on specific foreign particles. Rather than generically attack any antigens, T cells circulate until they encounter their specific antigen. As such, T cells play a critical part in immunity to foreign substances. The diagram below represents the process of CAR.

  1. T-cells are removed from the patient's blood.

  2. In a lab setting, the gene that encodes for the specific antigen receptors are incorporated into the T-cells.

  3. This produces the CAR receptors on the surface of the cells.

  4. The newly modified T-cells are then further harvested and grown in the lab

  5. After a certain time period, the engineered T-cells are infused back into the patient.

Different tools, gene circuits and synthetic receptors developed can be used to tackle some of the most important challenges that cellular immunotherapy is currently facing, namely

  • safety,

  • efficacy, and

  • manufacturing.

Different applications of synthetic biology in cancer cellular immunotherapy.

Cells can be reprogrammed with user-defined input-output relationships. This can be achieved via designing synthetic receptors.

Different chimeric antigen receptor (CAR) designs that can perform logic to enhance tumor specificity or to tune T cell activity. The tumor antigen is shown in dark gray.

Different CAR designs that can mitigate CAR/T cell–related toxicities. Infusion of CAR templates in cells can potentially lead to Tumor lysis syndrome which can be controlled by designing CAR designs that inhibit such behaviour.

Development of novel gene circuits or CARs to increase effectiveness of CAR T cell therapy by engineering T cell mobility or mitigating immunosuppressive cues (agents that suppress immune response) in the cancer microenvironment.

Engineering cells with gene circuits that can tune T cell activation and its duration. T cells divide rapidly and secrete cytokines that regulate or assist the immune response.