Recombinant adeno-associated virus-nadh dehydrogenase subunit 4 gene full-length and agent for the treatment of leber hereditary optic neuropathy

Abstract

The invention discloses a recombinant adeno-associated virus-NADH dehydrogenase subunit 4 gene full length and a medicament for treating Leber hereditary optic neuropathy. The full length of the gene is shown in the nucleotide sequence of SEQ ID NO: 1. Wherein, the nucleotide sequence has a full length of 3824bp, which consists of a CAG promoter sequence, a coding sequence of ND4 with a Cox10 mitochondrial localization sequence and a UTR with a length of 625bp. The medicament is injected into the vitreous cavity of the eye for the treatment of Leber's hereditary optic neuropathy. The medicament of the present invention is injected into the vitreous cavity, can maintain vitality in the vitreous cavity, and can be efficiently transfected into optic nerve cells. The signal peptide at the front end of the protein N, Orientation guides the protein into the mitochondria, and the mature ND4 protein enters the mitochondria to play a role. Therefore, drugs are effective in the treatment of Leber hereditary optic neuropathy.

Description

technical field [0001] The invention relates to the technical field of genetic engineering, in particular to a recombinant adeno-associated virus-NADH dehydrogenase subunit 4 gene full-length and a medicament for treating Leber hereditary optic neuropathy. Background technique [0002] Leber's hereditary optic neuropathy (Leber's hereditary optic neuropathy, LHON) is a disease caused by mitochondrial gene mutations. Leber's hereditary optic neuropathy is one of the world's recognized blindness in adolescents. It manifests as acute or subacute painless vision loss in both eyes at the same time or successively, and may be accompanied by central visual field defect and color vision disturbance. [0003] Scholars have confirmed that more than 20 mitochondrial mutation sites lead to the occurrence of LHON, including 11778, 14484, 3460, 3490 and so on. Among them, the 111778 site mutation is the most common, accounting for 89.2% of LHON in my country, and the prognosis is the wor...

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Problems solved by technology

But in practice, we found that the transfection efficiency of AAV2-ND4 in the previous study was low and could not achieve the purpose of treatment: since AAV2-ND4 needs to be injected into the vitreous cavity of the eye, it can be transfected to the optic nerve, but the vitreous cavity of the eye The amount of injection is limited, 0.1ml can be injected at most, and the dose is very small, resulting in very little normal ND4 transfected to the optic nerve. If the concentration of AAV-ND4 is increased, the body’s immune response will be caused, and repeated administration will also cause immune response. effect

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