Electrically regulated cell‐based intervention for viral infections

This work reports on an engineered cell that-when electrically stimulated-synthesizes a desired protein, that is, <i>ES-Biofactory</i>. The platform has been used to express interferon (IFN)-β as a universal antiviral protein. Compelling evidence indicates the inevitability of new pandemics and drives the need for a pan-viral intervention that may be quickly deployed while more specific vaccines are in development. Toward this goal, a fast-growing mammalian cell (<i>Chassis</i>) has been engineered with multiple synthetic elements. These include-(1) a voltage-gated Ca²⁺ channel (<i>Voltage-Sensor</i>) that, upon sensing the electric field, activates the (2) Ca²⁺-mediated signaling pathway (<i>Actuator</i>) to upregulate (3) IFN-β, via an engineered antiviral transgene (<i>Effector</i>), that is, <i>ES-Biofactory</i>➔<i>IFN-β</i>. The antiviral effects of the <i>ES-Biofactory</i>➔<i>IFN-β</i> have been validated on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells. The irradiated <i>ES-Biofactory</i>, that does not exhibit oncogenic capacity, continues to exert antiviral effect. The resulting <i>ES-Biofactory</i>➔<i>IFN-β</i> uses a novel signaling pathway that, unlike the natural IFN synthesis pathway, is not subject to viral interference. Once clinically validated, the <i>ES-Biofactory</i> will be a universal antiviral cell therapy that can be immediately deployed in the event of an outbreak. The platform may also be useful in treating other diseases including cancer and autoimmune disorders.