Modified Mitochondria With Adhesion Targeting for Cell Delivery
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Solution Overview
Problem
Current treatments for mitochondrial diseases caused by mutations in mitochondrial DNA are limited, and there is a need for effective cell or somatic gene therapy options.
Innovation Solution
Introduce an exogenous mitochondrion from a donor cell into a recipient cell by genetically modifying the donor cell to express a fusion protein that binds to an adhesion molecule on the recipient cell and includes a mitochondrial outer membrane targeting domain, allowing the mitochondrion to be introduced into the recipient cell.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mitochondrial transplantation is performed to treat mitochondrial diseases, then cellular function can be restored, but the complexity of the procedure and difficulty of delivery increase significantly
Solution Approach 1:
The invention uses an adhesion molecule-binding polypeptide as an intermediary to mediate between the mitochondrion and the recipient cell. This polypeptide binds to specific adhesion molecules on the cell surface, serving as a docking mechanism that facilitates mitochondrial entry without requiring complex surgical or surgical-like procedures, thus restoring cellular function while simplifying the transplantation process
Solution Approach 2:
The adhesion molecule-binding polypeptide is pre-installed on the mitochondrion surface before transplantation. This preliminary action of equipping mitochondria with targeting capabilities allows them to autonomously navigate and enter recipient cells, eliminating the need for complex external delivery systems or procedures during the actual transplantation
2Adaptability or versatility
If exogenous mitochondria are introduced into recipient cells, then mitochondrial DNA can be modified, but the difficulty of delivering intact mitochondria increases
Solution Approach 1:
The adhesion molecule-binding polypeptide acts as a mediator that bridges the gap between exogenous mitochondria and recipient cells. By binding to cell surface adhesion molecules, it facilitates the gentle entry of intact mitochondria into the cytoplasm, preserving mitochondrial integrity while enabling subsequent DNA modification through natural cellular processes
Solution Approach 2:
The invention changes the surface properties of mitochondria by attaching adhesion molecule-binding polypeptides. This parameter change in surface chemistry enables specific recognition and binding to cell surface receptors, transforming the delivery process from a complex mechanical challenge into a simpler biochemical recognition event
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
This method enables the delivery of healthy mitochondria to replace damaged ones, restoring cellular function and providing a means to modify mitochondrial DNA, addressing the limitations of existing treatments for mitochondrial diseases.
Implementation Method 1
a polypeptide capable of binding to an adhesion molecule on the recipient cell
Implementation Method 2
a polypeptide including a mitochondrial outer membrane targeting domain; wherein the modified mitochondrion includes the fusion protein positioned in the outer membrane of the modified mitochondrion
Data Source
AI summary
Methods and compositions for introducing an exogenous mitochondrion harvested from a donor cell into a recipient cell are provided. Also provided are methods and compositions for producing a modified mitochondrion and treating mitochondrial disease in an individual with the mitochondrial disease. Further provided are modified mitochondria, genetically modified mitochondria, genetically modified cells, isolated compositions and pharmaceutical compositions for practicing the subject methods.