Chemically Modified mRNA for CFTR Gene Delivery
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Solution Overview
Problem
Current treatments for diseases associated with the CFTR gene, such as cystic fibrosis, congenital absence of the vas deferens, and chronic obstructive lung disease, are ineffective and costly, with viral gene therapy approaches leading to immune reactions and insufficient hCFTR expression.
Innovation Solution
Chemically modified mRNA encoding the CFTR gene, complexed with PLGA-based nanoparticles, is administered intratracheally or intravenously to enhance stability, reduce immunogenicity, and achieve targeted expression of functional CFTR protein in lung tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viral vectors (adenoviruses or adeno-associated viruses) are used to deliver CFTR gene, then gene delivery is achieved, but immune reactions occur and hCFTR expression is insufficient
Solution Approach 1:
The patent uses chemically modified mRNA as an intermediary carrier to deliver CFTR gene information, avoiding direct viral vector delivery. The mRNA is complexed with biocompatible PLGA nanoparticles, which serve as a non-immunogenic delivery vehicle, thereby eliminating immune reactions while achieving sufficient hCFTR protein expression in lung tissues
Solution Approach 2:
The patent employs chemically modified nucleotides (such as pseudouridine, 5-methylcytidine, and N6-methyladenosine) to alter the chemical parameters of mRNA. These modifications enhance mRNA stability, reduce immunogenicity, and improve translation efficiency, thereby achieving reliable hCFTR expression without triggering immune responses
2Duration of action of stationary object
If repeated administration of viral vectors is performed, then gene delivery is maintained, but immune reactions worsen
Solution Approach 1:
The patent replaces repeated viral vector administration with repeatable mRNA nanoparticle delivery. The PLGA nanoparticle-mRNA complex serves as a reusable delivery system that can be administered multiple times without eliciting progressive immune responses, enabling sustained gene delivery over time
Solution Approach 2:
The patent uses transient mRNA molecules packaged in biodegradable PLGA nanoparticles as disposable delivery vehicles. Each administration provides temporary but sufficient hCFTR expression, and the nanoparticles degrade naturally after delivery, allowing repeated administrations without cumulative immune reactions
Data Source
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AI summary
The present invention relates to a chemically modified mRNA, a nucleic acid molecule encoding the CFTR cmRNA, a vector comprising said nucleic acid molecule, a host cell comprising said vector, a pharmaceutical composition comprising the CFTR cmRNA, nucleic acid molecule or vector, and to a method for the treatment of a disease associated with the CFTR gene.