Targeted Lipid Particles with Fusogen Proteins for Gene Delivery
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Solution Overview
Problem
Current methods for delivering lipid particles or viral vectors for gene therapy are limited by low efficiency and high toxicity, particularly when administered repeatedly.
Innovation Solution
The method involves administering repeated doses of targeted lipid particles or viral vectors, specifically engineered with fusogen proteins such as Paramyxovirus envelope proteins, to enhance targeting and fusion with target cells, thereby improving delivery efficiency and reducing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If repeated doses of lipid particles or viral vectors are administered, then gene delivery efficiency is improved, but toxicity increases
Solution Approach 1:
The patent modifies the temporal parameter of dosing by administering multiple doses within a compressed time window (within one month of each other, with specific intervals of 1-28 days). This parameter change in dosing frequency and timing improves gene delivery efficiency while the use of fusogen proteins mitigates the toxicity that would normally increase with repeated administration
Solution Approach 2:
The patent introduces fusogen proteins (specifically Paramyxovirus envelope proteins) as intermediary molecules that mediate the interaction between lipid particles/viral vectors and target cells. These fusogens enhance targeted fusion and entry, improving delivery efficiency while reducing off-target toxicity through more specific cellular uptake mechanisms
2Productivity
If higher doses are administered to improve delivery efficiency, then gene delivery efficiency is improved, but off-target toxicity increases
Solution Approach 1:
The patent applies local quality by using fusogen proteins that provide targeted recognition and fusion capabilities at specific cell types. This localization of functional activity to target cells allows efficient gene delivery to intended cells while minimizing off-target effects, as the fusogens confer cell-type-specific entry mechanisms rather than non-specific uptake
3Duration of action of moving object
If repeated administration is performed within a short time frame, then treatment frequency is improved, but accumulation of toxicity occurs
Solution Approach 1:
The patent implements periodic action by establishing a structured dosing schedule with repeated administrations at specific intervals (within 1-28 days, with examples including 1, 2, 3, 4, 5, 6, 7, 14, 21, or 28 days). This periodic regimen allows treatment frequency to be improved while the use of fusogen proteins and optimized dosing intervals prevent accumulation of toxicity by allowing recovery between doses
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 enhances the efficiency of gene delivery to target cells, reduces the overall dose required, and minimizes off-target toxicity, making it a more effective and safer method for repeated administration.
Implementation Method 1
the targeted lipid particle comprises one or more fusogen proteins
Data Source
AI summary
Provided herein are methods of repeated administration of a lipid particle or viral vector, such as for delivery of a payload gene, to a subject.