Modified Nucleic Acid Delivery via Parameter Changes
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Solution Overview
Problem
Existing methods for delivering nucleic acids into cells often induce an innate immune response, leading to cytokine and interferon production and cell death, making it challenging to achieve efficient protein production without triggering immune reactions.
Innovation Solution
Development of formulation compositions comprising modified nucleic acid molecules and delivery agents such as nanoparticles, lipids, and polymers that facilitate in vivo delivery of nucleic acids to targeted cells without inducing an immune response, using modified mRNA encoded with specific polypeptides and optimized delivery agents like PLGA microspheres and lipid nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If unmodified nucleic acid molecules are delivered into cells, then nucleic acid delivery is achieved, but innate immune response is induced leading to cytokine production and cell death
Solution Approach 1:
The patent applies parameter changes by chemically modifying the nucleic acid structure through 2'-O-methylation and 5-methylcytosine substitution. These structural parameter changes reduce the nucleic acid's recognition by immune sensors while maintaining its biological function, thereby delivering nucleic acids without triggering harmful immune responses
Solution Approach 2:
The patent uses composite materials by combining modified nucleic acids with delivery vehicles such as liposomes and polymers. This composite approach enables effective nucleic acid delivery while the delivery vehicle protects the modified nucleic acid from immune detection and facilitates cellular uptake
2Object-affected harmful factors
If modified nucleic acid molecules are used, then immunogenicity is reduced, but protein production efficiency must be maintained
Solution Approach 1:
The patent maintains protein production efficiency despite modifications by carefully selecting and positioning specific chemical modifications (2'-O-methylation at specific adenosine positions, 5-methylcytosine substitution). These parameter changes are designed to preserve the nucleic acid's ability to be translated into protein while reducing immune recognition
Solution Approach 2:
The patent applies local quality by implementing modifications at specific locations within the nucleic acid sequence rather than uniform modification throughout. This localized approach ensures that critical regions for protein production remain accessible while only specific immunogenic regions are modified
Data Source
AI summary
The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.