HES Oligonucleotide Complexes for Cellular Delivery
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Solution Overview
Problem
Current methods for delivering oligonucleotides, such as RNAi and antisense oligonucleotides, face challenges including low uptake by eukaryotic cells, sequestration, and degradation, limiting their therapeutic potential due to inefficient delivery across biologic barriers and triggering of innate antiviral defenses.
Innovation Solution
Development of H-type excitonic structure (HES) oligonucleotide complexes that link oligonucleotides, enabling efficient passive diffusion across cellular membranes and avoiding lysosomal degradation, thereby enhancing delivery and reducing toxicity and interferon response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional delivery vehicles (liposomes, lipid nanoparticles, cholesterol conjugates, antibody conjugates) are used to deliver oligonucleotides, then some delivery capability is achieved, but delivery efficiency across biologic barriers remains suboptimal
Solution Approach 1:
The patent applies parameter changes by modifying the physical-chemical properties of the delivery system through HES formation. The fluorophore aggregation state is changed from dispersed to aggregated, creating a specific supramolecular structure with altered membrane interaction properties that enables efficient cellular uptake and target accessibility
2Productivity
If high doses of oligonucleotides are administered to achieve therapeutic effect, then therapeutic efficacy is improved, but toxicity increases
Solution Approach 1:
The HES acts as an intermediary delivery vehicle that mediates between the oligonucleotide cargo and the cellular uptake machinery. The fluorophore aggregate structure serves as a membrane-penetrating carrier that protects the oligonucleotide and facilitates its transport into cells, enabling therapeutic efficacy at much lower doses with reduced toxicity
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 HES-oligonucleotide complexes achieve high-efficiency delivery into cells, reducing the required oligonucleotide dosage by orders of magnitude, minimizing toxicity, and effectively targeting nucleic acid sequences for therapeutic and diagnostic applications.
Implementation Method 1
the surprisingly high efficiency with which the non-toxic HES-oligonucleotide complexes of the invention are delivered into cells through sequence independent passive diffusion
Implementation Method 2
The invention relates to oligonucleotide complexes containing H-type excitonic structures (HES) and methods of making and using these complexes
Data Source
AI summary
This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.