University of Pittsburgh researchers have designed six antisense oligonucleotides (ASOs) to halt influenza viral replication. Unlike the current annual vaccinations, ASOs are designed to target highly conserved regions of the influenza virus. They also have the potential to target different strains of influenza acting as a universal treatment, reducing the need for annual vaccination and improving outcomes for patients.
Description
Influenza is responsible for as many as half a million deaths globally each year and between 5–20% of the US population will contract the virus annually. Current limitations of vaccines and treatments are often a driver for viral evolution. There is a great unmet need to develop universal treatment for influenza capable of targeting multiple strains and evading antigenic shift and drift.
Applications
1. Influenza
2. Negative sense RNA viruses
Advantages
Annual vaccinations against influenza exist but are developed months ahead of time based on a prediction on circulating strains of influenza. Even when this prediction is accurate the vaccine efficacy is only 60–80%. Additionally, only three licensed antivirals are available. These target surface proteins, neuraminidase, and are prone to viral evolution impacting on the effectiveness against multiple strains of influenza, and potentially linked to the emergence of treatment-resistant strains.
Through next-generation sequencing based approaches, new understanding of the regions of viral RNA critical to viral replication were discovered. ASOs targeting these regions have been identified. Given these ASOs target highly conserved regions of the influenza genome these will be able to target a wider variety of influenza strains including year-on-year evolution.
Invention Readiness
Previous research has found influenza viruses are composed of eight negative sense RNA segments, all of which must be incorporated to form a fully infectious virion. These RNA segments are bound by several copies of the structural nucleoprotein (NP) forming intra- and inter-segmental RNA-RNA interactions. Both types of interaction are vital for production of fully infectious viruses. Genome-wide maps have for the first time demonstrated that binding between NP and RNA exhibit a unique binding profile with some areas rich and others poor in NP. Six different ASOs of length 30–50 nucleotides have been designed to target against regions of viral RNA bound by NP forming RNA duplexes which could interfere with the replication of influenza viruses during infection. Work is now required to test the efficacy of these ASOs in interfering with influenza replication in multiple strains.
IP Status
https://patents.google.com/patent/US11046958B2
