Docket #: S11-234
Robust and Sustained Transgene Expression with Mini-Intronic Plasmid Vectors
Researchers in Prof. Mark Kay's laboratory have developed a robust vector that combines the ease of plasmid preparation with the stable expression achieved by minicircle vectors. This technology – Mini-Intronic Plasmids (MIP) – integrates essential bacterial elements for antibiotic-free selection and propagation within an engineered intron contained within a non-coding exon. MIPs offer an easy to implement alternative to minicircles for a variety of gene transfer/therapy, protein production and research applications where optimal transgene expression is required. In many cases, transgene expression is up to 10-times higher than that achieved by routine plasmids, minicircles or when used within a viral vector such adeno associated viral vectors (AAV).
Stage of Research
The inventors have demonstrated up to 10-fold higher in vivo transgene expression from MIP vectors than minicircle vectors in mouse livers. Biological materials are available for evaluation.
Applications
- Gene therapy - extrachromosomal expression of therapeutic genes without the risks associated with integration into patient genome
- RNA and protein production - synthesis of peptides, proteins and RNAs
- Robust AAV vector - robust transgene expression AAV vectors
- Research - vectors for creating transgenic cells and animals
Advantages
- Easy, scalable production:
- standard plasmid preparation for mass production
- RNA-out selection instead of antibiotic-selection
- Robust, prolonged expression:
- persistent expression at up to 10-fold higher levels than minicircles
- no bacterial plasmid-induced DNA silencing
- up to 10 fold enhanced AAV-mediated transgene expression
Publications
- Lu J, Zhang F, Kay MA. " A Mini-intronic Plasmid (MIP): A Novel Robust Transgene Expression Vector In Vivo and In Vitro " Mar 2013. Mol Ther 10.1038/mt.2013.33
- Published International Patent Application (pending) WO 2013/119371
Transgene expression in mice
DNA constructs injected into mouse livers showed luciferase expression from MIP vectors was 7-fold higher than plasmid vectors and 3-fold higher than minicircle vectors.
Related Links
Patents
- Published Application: 20130210897
- Published Application: WO2013119371
- Issued: 9,347,073 (USA)
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