Lipid Nanoparticle Composition for Stable Intracellular RNA Delivery
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Solution Overview
Problem
The effective targeted delivery of biologically active substances such as small molecule drugs, proteins, and nucleic acids to cells is hindered by their relative instability and low cell permeability, with existing lipid-containing nanoparticle compositions lacking in safety, efficacy, and specificity.
Innovation Solution
Development of novel lipid nanoparticle compositions comprising cationic and/or ionizable amino lipids, phospholipids, and PEG lipids, which are used to deliver therapeutic and prophylactic agents to mammalian cells or organs, with formulations that include specific fractions and are stored under refrigerated or frozen conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acids are delivered to cells using conventional methods, then delivery can be achieved, but the relative instability and low cell permeability of nucleic acids hinder effective delivery
Solution Approach 1:
The patent uses lipid nanoparticle compositions as intermediary vehicles to deliver nucleic acids to cells. The lipid nanoparticles protect the nucleic acids from degradation and facilitate their entry into cells, resolving the contradiction between delivery effectiveness and nucleic acid stability.
Solution Approach 2:
The patent employs composite lipid nanoparticle formulations containing multiple components including ionizable lipids, phospholipids, and PEGylated lipids. This composite material approach enhances both the stability of the nucleic acid cargo and the effectiveness of cellular delivery.
2Ease of operation
If lipid-containing nanoparticle compositions are used for delivery, then cell permeability is improved, but safety, efficacy, and specificity are still lacking
Solution Approach 1:
The patent optimizes parameters of the lipid nanoparticle compositions including the charge state of lipids (ionizable vs. cationic), the ratio of different lipid components, and the degree of PEGylation. These parameter changes enhance cell permeability while simultaneously improving safety and efficacy profiles.
Solution Approach 2:
The patent applies different lipid components with specific local functions: ionizable lipids for endosomal escape, phospholipids for membrane interaction, and PEGylated lipids for stability and reduced immunogenicity. This local quality differentiation resolves the contradiction between permeability and safety/efficacy.
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 novel lipid nanoparticle compositions enhance the safety, efficacy, and specificity of therapeutic and prophylactic delivery, effectively producing polypeptides and treating diseases such as rare diseases, cancer, and autoimmune diseases.
Implementation Method 1
Lipid-containing nanoparticle compositions, liposomes, and lipoplexes have proven effective as transport vehicles into cells and/or intracellular compartments for biologically active substances
Data Source
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AI summary
The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.