Liver Transgene Insertion Platform for Durable Therapeutic Protein Expression
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Solution Overview
Problem
Current gene therapy methods for conditions like hemophilia and lysosomal storage diseases are not radical or long-term, relying on temporary and repetitive administration of therapeutic agents, and there is a need for a platform that allows permanent expression of therapeutic genes in the liver for effective treatment.
Innovation Solution
A platform using the CRISPR-Cas system to insert a transgene into highly expressed and secretory genes in hepatocytes, enabling continuous expression of proteins of interest, such as therapeutic genes, to treat genetic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If temporary and repetitive administration of therapeutic agents is used, then treatment can be provided, but the treatment is not radical and long-term
Solution Approach 1:
The patent applies preliminary action by inserting the therapeutic transgene into the hepatocyte genome before the actual therapeutic effect is needed. The guide nucleic acid and editor protein are used to integrate the transgene at a predetermined genomic site, establishing a permanent therapeutic platform that will continuously produce the therapeutic protein without requiring repeated administrations
Solution Approach 2:
The patent implements self-service by enabling the liver to produce and secrete the therapeutic protein autonomously through the integrated transgene. The endogenous promoter drives continuous expression of the therapeutic gene in hepatocytes, which then self-regulate the production and secretion of the therapeutic protein without external intervention
2Duration of action of stationary object
If AAV is used for gene expression, then therapeutic gene expression can be achieved, but the expression is temporary and cannot provide long-term treatment
Solution Approach 1:
The patent uses preliminary action by pre-inserting the therapeutic transgene into the hepatocyte genome using guide nucleic acid and editor protein before the therapeutic effect is needed. This establishes a permanent genetic modification that will continuously produce the therapeutic protein throughout the liver's functional life
Solution Approach 2:
The patent implements self-service by utilizing the liver's own endogenous promoter to drive continuous expression of the therapeutic transgene. The hepatocytes autonomously produce and secrete the therapeutic protein without requiring external therapeutic agents or repeated administrations
3Duration of action of stationary object
If a platform allows permanent expression of therapeutic genes, then long-term treatment is achieved, but the platform complexity increases
Solution Approach 1:
The patent applies taking out by extracting and utilizing only the essential components needed for permanent gene expression: guide nucleic acid, editor protein, and transgene integration. By removing unnecessary complex delivery systems and focusing on direct genomic integration, the platform achieves permanence with minimal complexity
Solution Approach 2:
The patent implements universality by creating a platform that can treat multiple genetic disorders through a single integrated system. The same guide nucleic acid and editor protein can be used to insert different therapeutic transgenes at predetermined sites, making the platform versatile for various therapeutic applications without requiring separate complex systems for each disease
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The platform enables continuous high-level expression of therapeutic proteins in hepatocytes, providing a fundamental therapeutic agent for improving body functions and treating genetic disorders.
Implementation Method 1
A platform using the CRISPR-Cas system to insert a transgene into highly expressed and secretory genes in hepatocytes, enabling continuous expression of proteins of interest
Data Source
AI summary
Provided is a platform for expressing a protein of interest by artificially manipulating the liver, and more particularly, to a platform for alleviating or treating a genetic disorder or improving a body function by inducing expression by inserting a transgene (e.g., a therapeutic gene) which can function or be expressed normally, into a high-expression secretory gene, instead of a disease gene which functions or is expressed abnormally. The high-expression secretory gene includes the HP or APOC3 gene. The transgene includes one that is highly expressed using a promoter in a hepatocyte genome and is secretory out of the cell.