Formulated Lipid Particles for Oligonucleotide Delivery
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Solution Overview
Problem
Current methods for delivering oligonucleotides in vivo face challenges in selectively and efficiently targeting specific tissues, such as heart, lung, and muscle tissues, for RNA interference applications, due to limitations in existing delivery systems.
Innovation Solution
The development of formulated lipid particles (FLiPs) that conjugate oligonucleotides to lipophiles and aggregate them with emulsions or liposomes, specifically targeting heart, lung, and muscle tissues by utilizing a liposome component with triacylglycerol, phospholipids, glycerol, and lipid-binding proteins, enhancing tissue affinity and delivery efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vector-based delivery systems or high-pressure intravenous injections are used to deliver oligonucleotides, then delivery across plasma membranes can be achieved, but selective and efficient delivery to specific tissues remains insufficient
Solution Approach 1:
The patent applies local quality by modifying specific regions of the oligonucleotide molecule with different functional groups: hydrophobic moieties (cholesterol, fatty acids) for membrane interaction, hydrophilic moieties for solubility, and tissue-specific targeting ligands. This regional differentiation enables the single oligonucleotide molecule to achieve both efficient delivery and selective tissue targeting simultaneously.
Solution Approach 2:
The invention creates composite oligonucleotide structures by conjugating multiple types of moieties to the oligonucleotide backbone: hydrophobic groups for membrane penetration, hydrophilic groups for stability and solubility, and tissue-specific ligands for targeted delivery. This composite approach resolves the contradiction by integrating multiple functions into a single delivery system.
2Reliability
If chemically-modified oligonucleotides including cholesterol-conjugated and lipid encapsulated forms are used, then delivery capability is improved, but tissue-specific targeting remains limited
Solution Approach 1:
The patent achieves multi-functionality by designing oligonucleotides that simultaneously perform multiple roles: the hydrophobic moieties enable membrane penetration and cellular uptake, the hydrophilic moieties provide solubility and stability in circulation, and the tissue-specific ligands enable selective binding to target tissues. This universal design resolves the contradiction between general delivery capability and specific tissue targeting.
3Ease of operation
If conventional delivery methods are used, then oligonucleotides can be administered in vivo, but the largest obstacle for in vivo oligonucleotide therapeutics - delivery - remains unresolved
Solution Approach 1:
The patent introduces lipid emulsions as intermediary carriers that facilitate oligonucleotide delivery. The emulsion droplets serve as temporary vehicles that protect oligonucleotides during circulation, enhance their solubility, and facilitate their uptake by target tissues through natural lipid metabolism pathways, thereby resolving the delivery obstacle while maintaining ease of administration.
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
FLiPs enable efficient and specific delivery of oligonucleotides to heart, lung, and muscle tissues, effectively inhibiting target gene expression, thereby treating diseases associated with these tissues by mediating RNA interference.
Implementation Method 1
a liposome component with triacylglycerol, phospholipids, glycerol, and lipid-binding proteins
Data Source
AI summary
This invention relates to new formulated lipid particles (FLiPs) comprising at least one of a single or double stranded oligonucleotide, where the oligonucleotide has been conjugated to a lipophile and at least one of an emulsion or liposome to which the conjugated oligonucleotide has been aggregated, admixed or associated. These particles have surprisingly been shown to effectively deliver oligonucleotides to heart, lung and muscle where they effect gene silencing.