Method for treating adrenoleukodystrophy (ALD) through optimized expression of ABCD1 gene with lentiviral vector EF1alpha promoter

Abstract

The invention belongs to the technical field of genetic engineering, and particularly relates to a method for treating adrenoleukodystrophy (ALD) through optimized expression of an ABCD1 gene with a lentiviral vector EF1alpha promoter. Gene therapy of ALD is mainly realized by transfecting autologous hematopoietic stem cells (HSCs) of a patient carrying the ABCD1 gene under the EF1alpha promoter with an improved and optimized lentiviral vector, wherein the lentiviral vector carrying the ABCD1 gene can be injected directly into the brain according to actual conditions.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and in particular relates to a method for treating adrenoleukodystrophy by using a lentiviral vector EF1α promoter to optimize the expression of ABCD1 gene. Background technique [0002] Adrenoleukodystrophy (ALD) is a recessive hereditary lipid metabolism disease, because peroxisomes in the cells have an obstacle to the oxidation of VLCFA (very long chain fatty acid), so that VLCFA in the blood, white matter, A large amount of accumulation in the adrenal cortex and other organs and tissues can cause demyelination of the central nervous system and atrophy or dysplasia of the adrenal cortex. It is the most common peroxisome disease, mainly involving the adrenal gland and white matter of the brain. Onset in childhood or adolescence, the main manifestations are progressive psychomotor disturbance, vision and hearing loss and / or adrenal cortical insufficiency, etc. The incidence of this ...

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Problems solved by technology

However, if the expression level of ABCD1 gene is low in cells, the abnormal accumulation of VLCFA in the cytoplasm cannot be effectively removed.

[0004] At present, although there are many gene therapy methods using viral vectors for gene delivery at home and abroad, the gene delivery efficiency caused by different viral vectors or even different preparation methods of the same vector is significantly different, and the gene delivery efficiency will directly affect the therapeutic effect of the disease

At present, most of the methods of applying cell therapy to treat genetic diseases have low efficiency and only modify blood stem cells, so that the clinical effect of disease treatment has not been as expected. Therefore, there is an urgent need to maximize the efficiency of viral gene transfer and modification Multiple Stem Cell Approaches to Improve Curative Effects of Genetic Diseases

[0005] Institutions such as the Bluebird Company of the United States are also trying to use the lentiviral vector to carry the normal ABCD1 gene for gene therapy clinical trials on 17 cases of children with ALD. The data is now in the stage of collection, and the results currently show that the patients have a certain response to the treatment within two years. , but the overall effect is still relatively weak, and one patient lost the ability to move and speak, and other conditions are still under follow-up observation, so gene therapy for ALD disease is currently in its infancy

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