Stabilized 9- and 10-Segmented Influenza Viruses for Packaging Interference

The patent converts the harmful effect of viral mutation and resistance into a beneficial therapeutic mechanism. Defective interfering particles (DIPs) with truncated genomes are designed to exploit the virus's own replication machinery and packaging mechanisms. The DIPs compete with wild-type virus for packaging into virions, and when packaged, create non-infectious particles that interfere with viral spread. This approach converts the virus's ability to mutate and resist drugs into a mechanism where defective genomes are preferentially packaged and neutralized, providing strain-independent protection without selecting for drug resistance.

The patent creates copies of viral genome segments with intentional defects (truncations) that mimic natural defective interfering particles. These copied defective segments are designed to be recognized and packaged by the viral polymerase and packaging signals, but they lack essential coding regions. The copies compete with functional viral segments for incorporation into new virions, producing non-infectious particles that interfere with productive infection. This copying strategy provides broad protection against different influenza strains without requiring strain-specific matching.

The patent creates a universal antiviral mechanism that functions across multiple influenza strains without requiring strain-specific customization. The defective interfering particles use conserved viral packaging signals and replication machinery that are common to all influenza A viruses. The DIPs do not rely on strain-matched antigens but instead exploit fundamental viral processes (genome packaging, replication) that are conserved across strains. This provides broad-spectrum protection against diverse influenza variants, including emerging strains, without needing to update the therapeutic approach.

The patent segments the viral genome into functional and defective components, using the segmented nature of influenza's RNA genome to advantage. By introducing additional defective genome segments with truncated open reading frames but intact packaging signals, the system creates competition at the segment level during viral assembly. The defective segments are packaged along with or instead of functional segments, creating non-infectious particles. This segmentation strategy exploits the virus's own segmented genome structure to provide strain-independent interference.