Codon-Optimized Insulin Gene for Liver Expression
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Solution Overview
Problem
Current diabetes treatments, particularly for type 1 diabetes, are invasive, expensive, and fail to achieve long-term glycemic control, leading to significant morbidity and mortality, with existing gene therapy approaches facing challenges in insulin production and immune response.
Innovation Solution
A novel codon-optimized human insulin gene sequence is used in a recombinant adeno-associated viral vector, specifically optimized for liver expression, allowing for continuous endogenous insulin production through a single peripheral vein administration, enhancing insulin production by at least 10-fold compared to wild-type sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If wild type insulin gene sequence is used, then immune response is reduced, but insulin production levels are insufficient
Solution Approach 1:
The patent applies codon optimization to change the nucleotide sequence parameters of the insulin gene while maintaining the same amino acid sequence. This allows achieving high insulin production levels through optimized codon usage in the liver, while the resulting insulin protein remains identical to human insulin, thereby minimizing immune response.
2Reliability
If complicated ex-vivo cell manipulation protocols are used, then gene transfer efficiency improves, but treatment complexity and infection risk increase
Solution Approach 1:
The patent employs a self-complementary AAV vector that can directly transduce liver cells in vivo without requiring ex-vivo cell manipulation. The vector delivers the codon-optimized insulin gene directly to hepatocytes, which then autonomously produce insulin, eliminating the need for complex cell culture, transfection, and transplantation procedures.
Solution Approach 2:
The patent uses AAV8 vector as an intermediary to deliver the insulin gene directly to liver cells in vivo. This viral vector acts as a mediator that efficiently transfers the genetic material across cell membranes without requiring direct cell manipulation, thereby simplifying the treatment protocol while maintaining high gene transfer efficiency.
3Reliability
If regular insulin injections are administered, then glycemic control is achieved, but treatment is invasive and expensive
Solution Approach 1:
The patent enables the patient's own liver cells to produce insulin endogenously through in vivo gene delivery. This self-service approach eliminates the need for external insulin administration, allowing the body to autonomously regulate blood glucose levels, thereby providing continuous glycemic control without invasive injections and reducing long-term treatment costs.
Data Source
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AI summary
There is described a nucleic acid molecule comprising a nucleotide sequence encoding for a functional preproinsulin protein wherein the nucleotide sequence has at least 86% identity to the sequence of SEQ ID NO. 1. Also described are: vectors comprising the nucleic acid molecule for expressing the preproinsulin protein; host cells comprising the nucleic acid molecule or a vector; a transgenic animal comprising cells comprising the nucleic acid molecule or the vector; a pharmaceutical composition comprising the nucleic acid molecule or the vector; a method of treating diabetes comprising administering a therapeutically effective amount of the vector to a patient suffering from diabetes; the nucleic acid molecule for use in therapy; and the nucleic acid molecule or the vector for use in the treatment of diabetes.