Electrically regulated cell‐based intervention for viral infections
Abstract
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 Ca2+ channel (Voltage‐Sensor) that, upon sensing the electric field, activates the (2) Ca2+‐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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 15, 2022
- Source ID
- 10.1002/btm2.10434
Entities
People
- Harikrishnan Radhakrishnan
- Harold S Javitz
- Marvin A. Ssemadaali
- Parijat Bhatnagar
- Sherri L. Newmyer
Organizations
- Defense Advanced Research Projects Agency
- National Cancer Institute
- National Institute of Biomedical Imaging and Bioengineering
- SRI International