WP2 will develop three different programmable gene delivery platforms covering different payload sizes. We will re-engineer HIV integrase by fusion with CRISPR/Cas systems to generate lentiviral vectors with programmable insertion, which will enable site-specific integration of up to 9kb payloads. We will exploit homology-independent targeted integration strategy to convert AAV vectors into site-specific integration tools able to insert up to 4kb payloads in non-proliferating cells in vivo, such as the mouse retina and liver. We will work in combination with WP1 and WP4 to develop a safe harbour recombinase system, to enable site-specific delivery of payloads of unlimited size.
Specific WP’s objectives:
- Generation of programmable lentivirus
- AAV-mediated homology independent targeted integration in retina and liver
- Generation of safe harbor recombinase system
Tasks:
- Task 2.1: Engineering LV integrase to make it programmable and specific
- Task 2.2: Assemble LV particles including a programmable integrate
- Task 2.3: AAV-mediated homology independent targeted integration in the retina
- Task 2.4: AAV-mediated homology independent targeted integration in the liver
- Task 2.5: Development of a human safe harbor recombinase system
Timeline:
WP leader: Marc Guell (PFU)
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