Deuterated Polyribonucleotides for Low-Immunogenic Protein Expression
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Solution Overview
Problem
Polyribonucleotides used for protein synthesis in therapeutic contexts face challenges due to high immunogenicity and insufficient protein expression levels.
Innovation Solution
Incorporating deuterated nucleotides such as adenosine, cytidine, guanosine, and uridine into polyribonucleotides to reduce immunogenicity and enhance protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard nucleotides are used in polyribonucleotides, then the polyribonucleotide can be synthesized and introduced into cells, but it triggers considerable immunological reactions and shows insufficient stability
Solution Approach 1:
The patent applies parameter changes by substituting hydrogen atoms with deuterium atoms in the nucleotide structure. This isotopic substitution modifies the physical and chemical properties of the nucleotides, resulting in reduced immunogenicity and enhanced stability of the polyribonucleotide without altering its fundamental coding function
Solution Approach 2:
The patent creates a composite nucleotide structure by combining deuterated nucleotides with the polyribonucleotide backbone. This composite approach integrates modified nucleotide units into the overall polyribonucleotide molecule, achieving both reduced immunogenicity and maintained protein expression capability
2Object-affected harmful factors
If modified nucleotides are incorporated to reduce immunogenicity, then immunological reactions are reduced, but protein expression levels may be compromised
Solution Approach 1:
The deuterium substitution maintains the essential chemical bonding and structural properties of the nucleotides while changing their immunogenic characteristics. This selective parameter modification allows the polyribonucleotide to evade immune detection while preserving its ability to be translated into protein by cellular machinery
Solution Approach 2:
The deuterated nucleotides serve as isotopic copies of standard nucleotides, maintaining the same chemical identity and bonding behavior while possessing different physical properties. This copying approach ensures that the polyribonucleotide structure and function are preserved while immunogenicity is reduced
Data Source
AI summary
The present disclosure provides polyribonucleotides, in particular polyribonucleotides, which comprise deuterated adenosine, cytidine, guanosine, and/or uridine residues and which show reduced immunogenicity and/or enhanced expression, and methods of using such polyribonucleotides for the therapy of diseases.