Bioinformatic method to enhance gene expression and improve recombinant vaccines
This new bioinformatic method can be used to optimise sequences to improve stability and increase gene expression in RNA viral vectors. This could be applied to improve protein production yields from in vitro expression systems or in recombinant viral vaccines to increase antigen levels and thus improve immunogenicity. Importantly, this method does not change protein sequences and will not alter vaccine antigenicity or effectiveness.
Drug discovery & screening (allergy, anaphylaxis and autoimmune disorders)
Early stage proof of principle data & software tools available
Priority patent application (Ref.WO2014155076) filed March 2013
Licensing and/or collaborative research
Viral vectors are used in basic research as tools for efficient delivery and expression of proteins for further study. A number are also being used by pharma and biotech companies as vaccine delivery vehicles where the viruses are engineered to deliver and express pathogen proteins to stimulate protective immune responses. However the relationship between host and virus cells is complex, with host cells evolving to suppress virus replication and reduce expression levels from these sorts of vector. Methods that circumvent these effects and increase the efficiency and stability of these vectors in host cells are needed to improve their performance.
University of Edinburgh researchers have developed a new bioinformatic method to modify the sequence compositions of RNA viruses or other RNA sequences to maximize the level of protein expression and to reduce cellular toxicity. The invention is based on newly discovered constraints on RNA virus replication and mRNA expression that can be circumvented through reduction in frequencies or elimination of the dinucleotides UpA and CpG that influence cellular recognition and RNA turnover.
The technology has been effective in enhancing gene expression and replication in all viruses and replicons tested so far, including: human enterovirus, echovirus 7 [E7], the mouse cardiovirus TMEV (Theiler’s Murine Encephalomyelitis Virus), the hepatitis C virus replion. Expression has been increased by 10-fold or substantially greater depending on the virus used, when compared to wild type, without evidence for toxicity.
- Improved yield, reduced cost & quicker generation of protein
- Stronger immunological responses
- Quick optimisation of all sequences
Simmonds et al (2013) BMC Genomics 14, 610
Atkinson et al (2014) Nucleic Acids Res, 42, 4527-4545