Modified RNA Jet Injection for Protein Expression
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Solution Overview
Problem
Current RNA-based gene therapy and genetic vaccination methods face challenges due to the instability of mRNA, leading to limited protein expression and the need for repetitive administrations, as well as inefficient delivery of RNA into cells, which hampers therapeutic effectiveness.
Innovation Solution
A modified RNA with increased G/C content and optimized codons is administered via jet injection, enhancing protein expression by increasing the stability and delivery efficiency of the encoded protein, thereby achieving higher and sustained protein production compared to conventional needle injection methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional needle injection is used to administer RNA, then the injection process is simple and easy to perform, but the delivery efficiency of RNA into cells is low and protein expression is limited
Solution Approach 1:
The patent changes the physical parameters of the injection process by using jet injection technology that delivers RNA at high velocity (typically 60-100 meters per second) through a fine jet stream, transforming the conventional low-pressure injection into a high-velocity delivery system that penetrates skin and delivers RNA deep into target tissues with much higher cellular uptake efficiency
Solution Approach 2:
The patent employs hydraulic principles by using a liquid stream under high pressure to propel the RNA solution through the skin barrier. The jet injection device utilizes fluid dynamics to create a focused high-velocity stream that penetrates tissue and distributes RNA uniformly in the target area, overcoming the limitations of conventional needle injection
2Productivity
If unmodified RNA is used for gene therapy, then the RNA sequence is simple to design, but the RNA stability is poor leading to rapid degradation and limited protein expression
Solution Approach 1:
The patent applies local quality modifications by making specific changes to particular regions of the RNA molecule, such as adding a 5' cap structure and a poly(A) tail at the 3' end, and incorporating modified nucleosides at specific positions. These localized modifications enhance RNA stability and translation efficiency without requiring complete redesign of the entire RNA sequence
Solution Approach 2:
The patent creates a composite RNA structure by combining modified nucleosides (such as pseudouridine or 5-methylcytidine) with standard nucleotides, and by integrating additional functional elements like 5' caps and poly(A) tails. This composite approach enhances RNA stability and reduces immunogenicity while maintaining the coding sequence functionality
3Reliability
If RNA is administered by conventional injection, then the administration method is straightforward, but the delivery efficiency into target cells is insufficient hampering therapeutic effectiveness
Solution Approach 1:
The patent replaces the mechanical needle-based injection system with a jet injection system that uses high-velocity fluid dynamics to deliver RNA. This substitution eliminates the need for physical needle penetration and uses a focused liquid jet to propel RNA through the skin and into target tissues, achieving superior delivery efficiency through non-mechanical means
Data Source
AI summary
The invention relates to an RNA comprising at least one open reading frame (ORF) and comprising at least one modification, which increases the expression of the encoded peptide or protein. Furthermore, the invention relates to the medical use of such a modified RNA administered to a subject by jet injection. The invention relates further to a pharmaceutical composition and to a kit of parts comprising said modified RNA for administration by jet injection, preferably for use in the field of gene therapy and/or genetic vaccination. Additionally, the invention relates to a method for enhancing the (localized) expression of RNA-encoded peptides or proteins in the dermis or muscle (of a mammal) comprising administering the modified RNA by jet injection. And finally, the invention relates to a method of treatment comprising administering the modified RNA by jet injection to a subject in need thereof.