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, ES‐Biofactory. 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 (Chassis) has been engineered with multiple synthetic elements. These include—(1) a voltage‐gated Ca(2+) channel (Voltage‐Sensor) that, upon sensing the electric field, activates the (2) Ca(2+)‐mediated signaling pathway (Actuator) to upregulate (3) IFN‐β, via an engineered antiviral transgene (Effector), that is, ES‐Biofactory➔IFN‐β. The antiviral effects of the ES‐Biofactory➔IFN‐β have been validated on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected cells. The irradiated ES‐Biofactory, that does not exhibit oncogenic capacity, continues to exert antiviral effect. The resulting ES‐Biofactory➔IFN‐β uses a novel signaling pathway that, unlike the natural IFN synthesis pathway, is not subject to viral interference. Once clinically validated, the ES‐Biofactory 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.