Technology ID

Cas9 Protein Delivery with Lentiviral Vector Particles as a Therapy for Sickle Cell Disease

Lead Inventor
Uchida, Naoya (The University of Tokyo)
Haro Mora, Juan (NHLBI)
Tisdale, John (NHLBI)
Development Stages
Pre-clinical (in vivo)
Research Products
Lead IC

This technology includes efficient lentiviral gene delivery system for both guide RNA and Cas9 endonuclease as a method to cure sickle cell disease. Gene correction is an ideal gene therapy strategy for hereditary disease, including sickle cell disease. To deliver both guide RNA and Cas9 endonuclease into target cells, we used HIV-l based lentiviral vector system, which allows for efficient gene delivery in various cells, including hematopoietic stem cells and ES/1PS cells in this system, transgene expression cassettes can be integrated into genomic DNA in target cells, which results in long‐ term transgene expression. Out data demonstrate that Cas9/CypA fusion proteins can be delivered with lentiviral particles, and the Cas9 fusion proteins have an endonuclease function to induce GFP DNA double strand break.

Commercial Applications
Perform gene correction in the β-globin gene and/or BCL11lA gene knock-down in hematopoietic stem cells to induce fetal hemoglobin expression to cure sickle cell disease.

Competitive Advantages
In this system, much smaller size of viral genome is packaged in lentiviral particles, which should allow for more efficient gene/protein delivery with lentiviral vectors. ln addition, site-specific DNA break can be induced for a short term only, which should allow for safer genome editing by reduction of DNA damage in target cells.
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