The ability to deliver miRNAs or small interfering RNAs (siRNAs) in vivo has been a major hurdle in harnessing the power of RNA interference.
This platform technology employs RNA virus-like vectors to deliver functional small RNAs to any tissue of interest. Depending on the application desired, vectors can be enabled for spread and/or amplification and can be utilized effectively for the delivery of the RNAi molecule.
RNA virus-like vectors are assembled in vitro and can manufactured with an array of replicative capacities. These vectors do not result in an inflammatory response or in cytotoxicity but generate robust expression for a period lasting 2-10 days. Furthermore, as these vectors on RNA-based and are restricted to the cytoplasm, there is a) no risk of genomic integration and b) they are not subject to toxicities observed with DNA viruses due to saturation of the cellular miRNA
processing machinery.
Current Development Status
- Proof of concept completed utilizing a multitude of RNA viruses
Applications
- Virus-like Vectors:
- Short term expression of an RNAi species ~3 days
- Influenza A virus with limited replicative capacity have already been FDA approved – suggesting safety of this methodology
- Fully Replicative Vectors:
- Longer term expression of an RNAi species ~7 days
- Both:
- Effective method to deliver RNAi species in vivo
- Specific delivery of therapeutic payload (RNAi-based) to selected tissues
- Including the ability of crossing the blood brain barrier
- Change tissue tropism of vectors used for delivery of RNAi species
Advantages
- Efficient method to deliver RNAi species in vivo to any tissue
- Not subject to toxicities associated with DNA virus delivery
Publications
- Schmid et al. A versatile RNA vector for delivery of coding and noncoding RNAs. J Virol. 2014, 88(4):2333
- Varble et al. An in vivo RNAi screening approach to identify host determinants of virus replication. Cell Host Microbe. 2013 14(3):346
- Langlois R et al. In vivo delivery of cytoplasmic RNA virus-derived miRNAs. Molecular Ther. 2012 Feb;20(2):367-75
- Varble et al. Engineered RNA viral synthesis of microRNAs. Proc Natl Acad Sci USA 2010 Jun 22; 107(25):11519-24
Patent Status
- International Application PCT/US2011/039284 filed June 6, 2011
- Status: Published. International Publication No. WO 2011/156273
- Chinese Application 201180038540.3 filed June 6, 2011
- Status: Published. CN Publication No. CN1033068835A
- European Application 11792995.4 filed June 6, 2011
- Status: Pending. EP Publication No. EP2576581
- US Application 13/702,532 filed December 6, 2012
- Status: Published. US Publication No. US-2013-0209406-A1
- Foreign Applications Pending: CA, HK, JP filed June 6, 2011
Contact
Idoia Gamez, PhD, MBA
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7317