Modified RNA for Cell Reprogramming Without Genomic Integration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for altering cell phenotype or generating pluripotent cells often rely on exogenous DNA or viral vectors, which can cause unintended mutagenic effects and trigger a strong innate immune response, limiting their therapeutic utility and efficiency.
Innovation Solution
The use of synthetic, modified RNAs that are introduced into cells to express desired proteins or alter developmental potential, featuring modifications such as 5-methylcytidine and pseudouridine to reduce the innate immune response and enable sustained expression without genomic alterations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If exogenous DNA or viral vectors are used to alter cell phenotype, then desired protein expression is achieved, but unintended mutagenic effects and strong innate immune response occur
Solution Approach 1:
The patent extracts and eliminates the harmful DNA component from the reprogramming process by using only RNA molecules. The RNA encoding reprogramming factors is introduced without any viral vectors or genomic integration, thereby removing the source of mutagenic effects and reducing innate immune response while maintaining protein expression capability
Solution Approach 2:
The patent uses modified RNA molecules as an intermediary carrier to deliver reprogramming factors. These RNA molecules are designed with specific modifications (5-methylcytidine, pseudouridine) that act as mediators to reduce immune recognition while still enabling translation into functional reprogramming proteins
2Reliability
If exogenous DNA or viral vectors are used to alter cell phenotype, then desired protein expression is achieved, but unintended mutagenic effects occur
Solution Approach 1:
The patent extracts and eliminates the harmful DNA component from the reprogramming process by using only RNA molecules. The RNA encoding reprogramming factors is introduced without any viral vectors or genomic integration, thereby removing the source of mutagenic effects while maintaining protein expression capability
Solution Approach 2:
The patent employs transient RNA molecules that are naturally degraded by the cell after serving their purpose of translating reprogramming proteins. These short-lived RNA molecules fulfill their function and then disappear, leaving no permanent genetic alteration or mutagenic risk
3Duration of action of moving object
If standard synthetic RNA is used, then protein expression is achieved, but strong innate immune response limits sustained expression
Solution Approach 1:
The patent changes the chemical parameters of the RNA molecule by incorporating modified nucleosides (5-methylcytidine replacing cytidine, and pseudouridine replacing uridine). These parameter changes in the RNA structure reduce its immunogenicity while preserving its ability to be translated into protein, thereby enabling sustained expression
Solution Approach 2:
The patent converts the potential harm of RNA being recognized as foreign by the immune system into a benefit by using modified nucleosides that mimic endogenous RNA structures. This allows the RNA to evade immune detection while still performing its protein-coding function, effectively using the immune system's tolerance for self-like structures
Data Source
AI summary
Described herein are synthetic, modified RNAs for changing the phenotype of a cell, such as expressing a polypeptide or altering the developmental potential. Accordingly, provided herein are compositions, methods, and kits comprising synthetic, modified RNAs for changing the phenotype of a cell or cells. These methods, compositions, and kits comprising synthetic, modified RNAs can be used either to express a desired protein in a cell or tissue, or to change the differentiated phenotype of a cell to that of another, desired cell type.