The high frequency of RNA virus mutations and the outbreaks of emerging RNA viral infection are the challenging issues in public health. Developing a drug that can overcome viral mutations with a broad-spectrum anti-viral activity is an unmet need.
Scientists at National Taiwan University observe the RNA synthesis of RNA virus at mitochondria/endoplasmic reticulum (Mito/ER) spheres in the infected cells, accompanied by the leakage of a mitochondrial nuclease, ENDOG, to the cytosol. The study is published in Nature Communications.
ENDOG released from mitochondria is capable of degrading viral RNAs as an anti-viral factor. However, the dark side is that the released ENDOG is translocated to nuclei and causes nuclear DNA damages.
Researchers engineer an ENDOG anchoring on mitochondrial surface, namely MOM-ENDOG, which expression efficiently degrades the viral RNA transcripts synthesized at mitochondrial sites without causing nuclear DNA damages. Delivery of modified mRNA encoding wild-type but not catalytic-dead MOM-ENDOG markedly suppresses the propagation of VSV, Influenza, Dengue, and Zika virus.
“This modified mRNA encoding mitochondrial site-specific viral RNA degrader is a broad-spectrum anti-viral agent and its mode of action would not be affected by the viral mutations,” says corresponding author Zee-Fen Chang, chair professor at Center of Nucleic Acid Medicine, National Taiwan University College of Medicine.
Prof. Zee-Fen Chang's email: [email protected]
