Gene Therapy Vector with Secretory Leader Sequence for CNS Delivery
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Solution Overview
Problem
Current gene therapy methods for neurological disorders face challenges such as low efficiency of gene delivery to the CNS, requiring large vector doses and risking immune reactions and insertional mutagenesis, with viral vectors often causing adverse side effects like cancer.
Innovation Solution
A modified gene therapy vector comprising a nucleic acid coding for a secretory leader sequence linked to a protein transduction domain (PTD) and a therapeutic protein, which reduces the viral load and number of infections needed by secreting the therapeutic protein outside genetically modified cells, allowing it to be internalized by non-modified cells, thereby amplifying the therapeutic effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If large vector doses are used to achieve effective gene delivery to the CNS, then therapeutic effectiveness is improved, but immune reactions and insertional mutagenesis risks increase
Solution Approach 1:
The patent uses a secretory leader sequence as an intermediary mechanism to enable therapeutic protein secretion from transduced cells. This mediator allows the therapeutic protein to be released into the extracellular space and taken up by non-transduced cells, thereby amplifying the therapeutic effect without requiring higher vector doses, thus avoiding immune reactions and insertional mutagenesis risks associated with high-dose viral vector administration.
2Productivity
If viral vectors are used to deliver genes to the brain, then gene delivery efficiency is improved, but adverse side effects like cancer and immune reactions occur
Solution Approach 1:
The patent extracts the therapeutic protein from the viral vector system by enabling its secretion into the extracellular space. The secretory leader sequence allows the therapeutic protein to be produced by transduced cells and released outside the cell, where it can be taken up by non-transduced cells. This extraction approach reduces the need for high viral vector doses, thereby minimizing adverse side effects like cancer and immune reactions while maintaining effective gene delivery to the brain.
3Area of stationary object
If multiple injections are used to create pockets of transgene expression throughout the brain, then widespread gene delivery is achieved, but treatment complexity and number of procedures increase
Solution Approach 1:
The patent implements a self-service mechanism where transduced cells automatically secrete the therapeutic protein into the extracellular space. This secreted protein then diffuses and is taken up by surrounding non-transduced cells, creating a self-propagating therapeutic effect that spreads throughout the brain tissue. This self-service approach eliminates the need for multiple injections to achieve widespread gene delivery, as the therapeutic effect naturally extends beyond the initially transduced cells.
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 approach significantly increases the distribution and effectiveness of therapeutic proteins in the CNS, reducing the need for high vector doses and minimizing side effects, making it safer and more efficient for brain gene therapy.
Implementation Method 1
the produced therapeutic protein, due to the secretory leader sequence is vehiculated outside the genetically modified cell
Implementation Method 2
due to the PTD, is internalized in cells that are not genetically modified
Data Source
AI summary
The present invention provides a new vector for gene therapy said vector being therapeutically very efficient, viral particles comprising said vector, compositions comprising said viral particle, uses thereof, methods for the preparation of the vector), and therapies using said vector.