Lentiviral vector suitable for gene therapy of thalassemia and sickle anemia

Abstract

The invention discloses a lentiviral vector suitable for gene therapy of thalassemia and sickle anemia. The lentiviral vector comprises a beta globin expression cassette; the expression cassette comprises a micro-locus control area, a gene sequence of a beta globin, a promoter sequence of a flank of the upstream of the gene sequence of the beta globin, and a flanking sequence of the downstream ofthe gene sequence of the beta globin; the micro-locus control area is a micro-control element which is screened out from the locus control area of beta globin 16kb and does not contain an HS1 area. Compared with the prior art, the screened beta globin expression cassette has both efficiency and specificity, and does not cause reduction of lentivirus titer; a screened insulator sequence which comesfrom foamy virus and is only 36 bp does not contain a hidden RNA splicing signal, and has the functions of maintaining gene expression and preventing gene activation in a region where the insulator sequence is located; the lentiviral vector can be used for gene therapy of thalassemia and sickle anemia.

Description

technical field [0001] The invention belongs to the field of medical technology, and in particular relates to a lentiviral vector suitable for gene therapy of thalassemia and sickle-cell anemia. Background technique [0002] So far, more than 7,000 rare diseases have been discovered in humans, but only 5% of the rare diseases have drugs available. Currently, almost all rare disease drugs require lifelong use. Gene therapy offers the possibility of a one-time cure for rare diseases. Thalassemia (thalassemia) is a monogenic hereditary hemoglobinopathy with the widest distribution and the largest cumulative patient population in the world. It is the most common human hereditary disease among rare diseases. [0003] The safety of gene therapy is the premise that it can become a routine therapy and benefit more patients. Lentiviral vectors are inserted into the genome in an uncontrolled manner (about 75% are integrated into transcriptionally active gene coding regions), accomp...

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Problems solved by technology

For example, a mini-locus (miniLCR) consisting of core elements of HS4, HS3, HS2 deoxyribonuclease I hypersensitive sites resulted in a significant reduction in viral titer (Weber, L. et al. AnOptimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype. Mol The Methods Clin Dev 10, 268-280 (2018)

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