Lentiviral vector applicable to gene therapy of thalassemia and sickle anemia

Abstract

The invention discloses a lentiviral vector suitable for gene therapy of thalassemia and sickle anemia. The system comprises: a, a micro locus control region, which is a micro regulatory element which is screened from a locus control region of beta globin 16kb and does not contain an HS1 region; b, a gene sequence of beta globin, wherein the gene sequence is as shown in SEQ ID NO.3; c, a promoter sequence of an upstream flanking of the gene sequence of beta globin; d, a flanking sequence at the downstream of the gene sequence of beta globin; and e, an insulator sequence from a Foamy virus (Foamy virus). Compared with the prior art, the invention optimizes the structure of the vector, and finds that after the second intron of the Beta globin gene (HBB) is optimized, the expression of the gene can be improved to a certain extent, and the packaging yield of the virus can be greatly improved, so that the clinical use and industrialization of the Beta globin gene become possible.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering and relates to a lentiviral vector, in particular 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 good safety of gene therapy is the prerequisite for it to become a routine therapy and benefit more patients. Lentiviral vectors are inserted into the genome in an uncontrolled manner (about 75% are integrated into transcripti...

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Problems solved by technology

[0007] In the prior art, the use of lentiviral vectors in the gene therapy of thalassemia and sickle cell anemia has potential safety hazards and is not very efficient; the purpose of the present invention is to solve the problem that the titer of the vectors in the prior art is too low to reach the level of clinical application; Insufficient expression, unable to achieve a therapeutic effect; and the lack of insulator sequences in the carrier, which easily activates the expression of adjacent genes, and has defects such as greater safety risks, providing a lentiviral vector suitable for gene therapy of thalassemia and sickle cell anemia

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