Human-derived single-chain insulin analogue and application thereof

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a human single-chain insulin analogue and application thereof, and the human single-chain insulin analogue comprises a sequence coding fragment as shown in SEQ ID NO.2, SEQ ID NO.3 or SEQ ID NO.4. The invention also relates to a preparation method of the human single-chain insulin analogue. The insulin analogue is obtained by replacing C peptide with flexible peptide and selectively changing the coding direction of a sequence, and the gene of the insulin analogue can generate high-activity human single-chain insulin in skeletal muscle cells, is independent of beta cells and has wide use modes.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a human-derived single-chain insulin analog and its application. Background technique [0002] Diabetes is an autoimmune disease caused by the loss or dysfunction of insulin-producing β-cells in the pancreatic islets, but the exact etiology and pathogenesis are unclear, and it may be a combination of genetic and environmental factors. Complications of diabetes, such as chronic hyperglycemia, systemic metabolic failure, and multiple organ damage, create a huge medical and social burden and lead to premature death of patients. There is currently no drug treatment that can effectively stop or reverse the progression of the disease, and the main treatment modality is insulin injections. [0003] Preproinsulin has 108 amino acids, the signal peptide is cleaved in the endoplasmic reticulum to form proinsulin, and proinsulin undergoes a one-step cleavage process by PCas...

AI Technical Summary

Problems solved by technology

The binding of proinsulin without protease hydrolysis to the insulin receptor is very weak, and its biological activity is only 5% of that of mature insulin. PC enzyme mainly exists in pancreatic β cells, so expressing natural insulin sequences in other target cells cannot form highly active insulin. insulin

Therefore, external insulin injection is required for treatment. Currently, there are two mainstream insulin production technologies in the world. The first is Novo Nordisk’s Saccharomyces cerevisiae expression system, and the second is Eli Lilly’s E. coli expression system, but both have production barriers : (1) The production process is complicated. Insulin has two chains, and the two chains are expressed through a polypeptide chain, which is called a precursor. After expressing one chain, it needs to be digested, purified, connected, etc. to form a double-chain structure ; (2) High requirements for cost control

[0004] T1D patients need life-long insulin replacement therapy from the beginning of diagnosis, and the global burden of diabetes is huge and growing. Insulin injections bring economic and psychological burdens and inconvenience to patients.

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