APPLICATIONS OF TECHNOLOGY:
- Medical: Pharmaceuticals
- Present strain is among the most robust constituents of the gut microbiome
- Obviates the need for exogenous iron-sulfur cluster producing genetic elements
In 2018, Gizzi et al. demonstrated that the human gene Viperin can produce antiviral small molecules (ddhCTP) that act as a chain terminator for RNA viruses. However, the described study for this broad-spectrum antiviral agent was challenging to scale and technically difficult, as it required anaerobic environments in addition to iron and sulfur. Researchers at the Berkeley Lab have overcome such issues by engineering a gut commensal microbe, Bacteroides thetaiotaomicron, to produce ddhCTPs. To their knowledge, there has been no precedence for a gut commensal microbe that is capable of making small molecules to suppress human viral infection.
The novel approach was achieved by heterologous expression of synthetically modified human proteins. Researchers chose to express the Viperin protein in B. thetaiotaomicron due to its anaerobic requirement and iron-sulfur cluster-rich metabolism. HPLC-UV Vis and High Resolution LC-MS revealed that this microbe produces ddhCTP in vivo without the need for auxiliary plasmids.
Applications of the invention include the colonization of human or animal GI tracts to prophylactically suppress RNA virus infections – among the most dangerous viruses known to date. It would provide the most therapeutic benefit to individuals highly prone to viral infections or in situations in which there is a great risk for contracting viral infections. Additionally, the present strain could be used for industrial production of ddhCTP and other nucleoside derivatives using B. thetaiotaomicron as a chassis.
DEVELOPMENT STAGE: Proven principle
FOR MORE INFORMATION:
STATUS: Patent pending. Available for licensing or collaborative research.
SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:
Influences on Gut Microbiome 2017-039