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.