This technology takes advantage of the species-specific expression of miRNAs to generate live attenuated influenza virus vaccines (LAIVs) alleviating all manufacturing constraints and the necessity of relying on cold-adapted mutants.
This technology is enabled by the silent insertion of perfect miRNA target sites to control the level and location of virus replication. Insertion of miRNA 
target sites can impose attenuation in a cell- and/or –species specific manner and has been successfully applied for vaccine development, manipulation of tropism to improve on antigen presentation, and as a means of molecular biocontainment. The idea is simple, insertion of target sites results in a virus or vector that can only replicate in cells lacking that miRNA (see Figure). If the miRNA is ubiquitous the virus demonstrates no replication. Despite extensive attempts, we have yet to find evidence of escape following targeting of influenza A virus.
Current Development Status
- Technology enabled in in vivo models using highly pathogenic influenza A viruses
Applications
- Novel LAIV based on microRNA-mediated gene silencing
- Potential for combination with existing LAIVs – improve safety
- This approach can also easily be adapted to tissue culture through the exploitation of miRNAs that are absent in select cell lines
Advantages
- Safe method of generating attenuated viral strains that grow at high titer in vitro or in ovo, while being attenuated in vivo in a specific species (e.g. pigs, dogs, horses, humans, other mammals)
- The degree of attenuation can be modulated by varying the number of MREs and/or the miRNA(s)
Publications
- Perez JT., et al. MicroRNA-mediated species-specific attenuation of influenza A virus. Nat Biotechnol. 2009 Jun;27(6):572-6
- Langlois R. et al. MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nat Biotechnol. 2013 Sep;31(9):844-7
Patent Status
- International Application PCT/US2010/000709 filed March 8, 2010
- Status: Published. International Publication No. WO 2010/101663
- Canadian Application 2,754,826 filed March 8, 2010
- Status: Pending
- Japanese Application 2011-552950 filed March 8, 2010
- Status: Published. JP Publication No. 2012-519484
- European Application 10749069.0 filed March 8, 2010
- Status: Published. EP Publication No. 2403527
- US Utility Application 13/255,040 filed February 23, 2012
- Status: Issued. US Patent No. 8,883,995
Contact
Idoia Gamez, PhD, MBA
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7317