Modified RNA Nucleotides for Reduced Immune Response
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for delivering nucleic acids to cells, tissues, and patients are inefficient, unstable, and trigger a potent innate-immune response, while RNA-based reprogramming methods are slow, unreliable, and require multiple transfections, making them undesirable for therapeutic or cosmetic use.
Innovation Solution
The use of safe and effective doses of nucleic acid drugs, including RNA with non-canonical nucleotides, administered through specific formulations and delivery methods to achieve significant and lasting protein expression with minimal toxicity and immune reaction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If synthetic RNA molecules are administered for therapeutic use, then protein expression is achieved, but the RNA molecules are unstable and trigger a potent innate-immune response
Solution Approach 1:
The patent modifies the chemical structure of RNA molecules by incorporating non-canonical nucleotides and modifying existing nucleotides (such as pseudouridine, 5-methylcytidine, and other modified bases). These parameter changes in the molecular structure reduce immunogenicity while maintaining or enhancing protein expression stability and efficiency
Solution Approach 2:
The patent creates composite RNA molecules that combine canonical and non-canonical nucleotides in specific ratios and configurations. These composite structures leverage the beneficial properties of different nucleotide types to achieve both stable protein expression and reduced immune activation
2Reliability
If RNA-based reprogramming methods are used to reprogram cells, then cell reprogramming is achieved, but the methods are slow, unreliable, and require multiple transfections
Solution Approach 1:
The patent employs pre-optimized RNA formulations with specific nucleotide modifications and delivery vehicle compositions that are prepared in advance to maximize cellular uptake and translation efficiency. This preliminary optimization eliminates the need for multiple transfection attempts and accelerates the reprogramming process
Solution Approach 2:
The patent modifies key parameters including RNA sequence design, nucleotide composition ratios, modification types and positions, and delivery vehicle characteristics to enhance reprogramming efficiency and reduce the time required for successful cell reprogramming
3Reliability
If existing synthetic RNA technologies are used, then protein expression is achieved, but the methods are inefficient and carry mutation risks
Solution Approach 1:
The patent optimizes manufacturing parameters including in vitro transcription conditions, nucleotide incorporation ratios, purification protocols, and formulation compositions to achieve high-yield production of modified RNA molecules with consistent quality and reduced impurities that could cause mutations
Data Source
AI summary
The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.