Live Attenuated Virus Platform Using miRNA Recognition Sequences
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Solution Overview
Problem
Live attenuated vaccines face safety concerns that limit their use across species, particularly in mammalian and avian populations, due to the lack of microRNAs that can effectively attenuate virus replication in these species without being present in vaccine production systems.
Innovation Solution
A microRNA-mediated vaccine platform is developed using a cell line deficient in universally expressed microRNAs, such as miRNA-21, and a modified virus with recognition sequences for these microRNAs, allowing for the production of live, attenuated viruses that are safely used across species by restricting replication in cells expressing the cognate microRNAs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated vaccines are used to provide robust protection against virus challenges, then vaccine efficacy is improved, but safety concerns arise due to potential zoonotic transmission and viral reassortment
Solution Approach 1:
The patent extracts the harmful replication capability of the virus by introducing miRNA recognition sequences that prevent the virus from replicating in mammalian and avian cells. The virus is stripped of its ability to cause disease while retaining immunogenicity, effectively separating protective function from harmful function.
Solution Approach 2:
The patent introduces miRNA recognition sequences as an intermediary mechanism that mediates between the vaccine virus and host cells. These sequences act as molecular barriers that allow the virus to stimulate immunity without enabling replication in non-target species, thus mediating safety while preserving efficacy.
2Reliability
If live attenuated vaccines are used to provide robust protection, then vaccine efficacy is improved, but the risk of viral reassortment increases
Solution Approach 1:
The patent removes the reassortment hazard by incorporating miRNA recognition sequences that prevent the virus from completing its replication cycle. Without replication, the virus cannot undergo reassortment with endogenous viruses, effectively extracting the reassortment risk while preserving the vaccine's protective capabilities.
3Ease of manufacture
If conventional cell lines are used for virus production, then manufacturing is simplified, but the virus can replicate in mammalian and avian species posing safety risks
Solution Approach 1:
The patent applies local quality by modifying specific regions of the virus genome to include miRNA recognition sequences. These localized modifications create species-specific restrictions on viral replication without affecting the overall manufacturing process, allowing conventional cell lines to be used while preventing cross-species transmission.
Solution Approach 2:
The patent changes the molecular parameters of the virus by introducing miRNA recognition sequences that alter the virus's host range. This parameter change restricts replication to species lacking the cognate miRNAs, maintaining ease of manufacture while eliminating cross-species safety risks.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables the creation of safe and effective live, attenuated vaccines that provide robust protection against lethal virus challenges without risking zoonotic transmission and reduces the risk of viral reassortment, allowing for broad species attenuation including mammals and birds.
Implementation Method 1
The influenza virus further comprises a miRNA-21 recognition nucleic acid sequence... the miRNA-21 has the sequence shown in SEQ ID NO:13... the miRNA-21 recognition nucleic acid sequence has the sequence shown in SEQ ID NO:14
Data Source
AI summary
This disclosure provides live, attenuated viruses, and methods of making and using the live, attenuated viruses.