Synthetic RNA Nucleotide Design for Reliable Somatic Cell Reprogramming
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Solution Overview
Problem
Existing RNA-based reprogramming and gene editing methods are inefficient, unreliable, and carry mutation risks, particularly when used in adult cells, requiring multiple transfections, immunosuppressants, and human-derived components, limiting their therapeutic applications.
Innovation Solution
Development of synthetic RNA molecules with low toxicity and high translation efficiency, incorporating non-canonical nucleotides like 5-methylcytidine and 7-deazaguanosine, for high-efficiency transfection, reprogramming, and gene editing, avoiding exogenous DNA and animal-derived materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing RNA-based reprogramming methods are used, then cells can be reprogrammed, but the process is inefficient and unreliable requiring multiple transfections
Solution Approach 1:
The patent modifies the chemical parameters of RNA by incorporating non-canonical nucleotides (5-methylcytidine, 7-deazaguanosine) to change the physical-chemical properties of the RNA molecule, thereby improving translation efficiency and reducing toxicity without requiring multiple transfections
Solution Approach 2:
The patent creates a composite RNA structure by combining canonical and non-canonical nucleotides in specific ratios and positions, forming a hybrid RNA molecule that leverages the advantages of both canonical (structural integrity) and non-canonical (translation efficiency, reduced immunogenicity) components
2Reliability
If existing RNA-based gene editing methods are used, then gene editing can be performed, but mutation risks increase and fidelity decreases
Solution Approach 1:
The patent changes the nucleotide composition parameters of RNA to include 5-methylcytidine and 7-deazaguanosine, which modify the RNA's interaction with cellular machinery, reducing off-target effects and mutagenesis while maintaining on-target editing efficiency
Solution Approach 2:
The patent converts the potential harm of RNA immunogenicity and toxicity into a benefit by using non-canonical nucleotides that reduce immune recognition and cellular toxicity, thereby improving the safety profile of gene editing while maintaining efficacy
3Ease of operation
If exogenous DNA is introduced for reprogramming, then reprogramming can occur, but mutation risks increase
Solution Approach 1:
The patent extracts and eliminates the harmful element (exogenous DNA) from the reprogramming process by using RNA alone, which can be delivered without integration into the host genome, thereby maintaining reprogramming capability while removing the risk of genomic mutations
Solution Approach 2:
The patent uses RNA as an intermediary molecule that can deliver reprogramming information without permanently altering the host genome, allowing transient expression of reprogramming factors without the risks associated with DNA integration
Data Source
AI summary
The present invention relates in part to nucleic acids encoding proteins, therapeutics comprising nucleic acids encoding proteins, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described.