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Transposagen Q3 2012 Overview
Transposagen Biopharmaceuticals provides advanced genetic modification technologies and services for creating better disease models, specializing in custom and off-the-shelf products using the PiggyBac transposon system and XTn TAL nucleases. Their offerings include gene editing, cell line engineering, and animal model creation, highlighting non-viral safety, high integration efficiency, and large cargo capacity. Applications range from gene therapy to drug discovery and biologics production, with a focus on improving research outcomes and therapeutic options.
Transposagen Q3 2012 Overview
- 1. Better Models. BetterResults™ Genetic Modification for Better Disease Models™ 1 © Transposagen Biopharmaceutics, Inc.
- 2. About Us Transposagen Biopharmaceuticals, Inc., is Technologies: dedicated to providing better disease models through genetic modification. • piggyBac™ Transposagen specializes in custom and off •XTN™ TAL Target-Specific the shelf XTN™ TAL Nucleases, animal models, cell lines, stem cells and cutting- Nucleases edge research tools and technologies to •Rodent Stem Cells improve drug discovery and development research. These unique technologies and services for genetic modification give Applications: customers and technology users access to •Rodent Model Creation any genetic modification in any gene in any genome for both research and biologic •Cell Line Engineering & Stem production purposes. Cells •Genetically Engineered Plants •Biologics Production •Therapeutics © Transposagen Biopharmaceutics, Inc.
- 3. piggyBac Site SpecificGenetic Engineering • Not limited to TTAA sites • Xanthamonas TAL nuclease (XTN: a.k.a TALENs) • TAL DNA binding modules and FokI DNA-cleavage domain • Site specific knockout, knock-in of any gene, any genome • Automated synthesis of XTNs • Remove transposon after gene editing © Transposagen Biopharmaceutics, Inc.
- 4. XTN™ TAL NucleaseKO Efficiency • Rag1 XTN target site amplified, cloned and sequenced • 16% disruption at the target site: better than Zinc-finger Nuclease and Meganuclease • Disruption sequences are shown below with XTN target site highlighted in grey © Transposagen Biopharmaceutics, Inc.
- 5. Site Specific Knock-in A.Site specific binding and induced dsDNA breaks B. Transfect SSCs C. Nested PCR confirmation of Homologous Recombination events © Transposagen Biopharmaceutics, Inc.
- 6. The piggyBac™ TransposonSystem Key Features •Efficient transgenesis using transfection •Titratable number of integrations •Large cargo limit – 10 to 100kb •Rapid identification of integration site •Reversible transposition – no footprint •All-in-one inducible vector •Safe non-viral system © Transposagen Biopharmaceutics, Inc.
- 7. piggyBac vs. ViralVectors Characteristic Viral Vectors piggyBac Safety X Induced Immune Response X Oncogene Activation X Production Costs X Cargo Capacity X Cargo Capacity (kb) Adenoassociated Virus Retrovirus Lentivirus piggyBac 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Source: Current Gene Therapy (2004), 4, 357-372 120 kb • Cargo capacity greater than 120 kb • Delivery of entire BACs reported © Transposagen Biopharmaceutics, Inc.
- 8. piggyBac™ Cumate InducibleSwitch Titratable and can turn back off easily © Transposagen Biopharmaceutics, Inc.
- 9. Reversible Transposition Pop-out thetransposon © Transposagen Biopharmaceutics, Inc.
- 10. Targeted Integration andExcision • Gene Therapy • Cell Lines Animal Models Therapeutics Cell Lines Bradley et al Nature (2011) In Press © Transposagen Biopharmaceutics, Inc.
- 11. Therapeutic Applications • Geneand Cell Therapy • Immunotherapy PB kills ovarian cancer cells of tumor xenografts in mice PB/TK cells stained red Apoptotic cells stain green Merged cells are yellow © Transposagen Biopharmaceutics, Inc.
- 12. Animal Models • Knockout • Knock-in • Transgenic • Transgenic knockdown Overexpression • Humanized • Conditional Rat and mouse models available Any species possible © Transposagen Biopharmaceutics, Inc.
- 13. Creation of AnimalModels using SSCs Figures Courtesy of Dr. Kent Hamra © Transposagen Biopharmaceutics, Inc.
- 14. Genetic Modification TechnologyComparison Primary Virus ZFN & HR Plasmid piggyBac & XTN Technology High Efficiency Yes No No Yes Non-viral safety No Yes Yes Yes Integration No Yes No Yes control Unlimited DNA No No No Yes Cargo size Reversible No No No Yes footprint free Site specific No Yes No Yes gene editing Cell lines and Yes Yes No Yes Animal Models Licensing No Yes No No restrictions © Transposagen Biopharmaceutics, Inc.
- 15. Custom Services Overview •Gene editing with XTNs (talens), HR vector, piggyBac Transposon Site specific knockout, knock-in, edit and correction of any gene in any genome • Stable cell lines Overexpression, knockdown, reporter lines, iPS reprogramming, iPS and ES differentiation and selection, therapeutic applications • Animal models Rat and mouse model generation available, additional species possible © Transposagen Biopharmaceutics, Inc.
- 16. Contact Information Jack Crawford,MS Director, Business Development jcrawford@transposagenbio.com © Transposagen Biopharmaceutics, Inc.