Modified miRNA Nucleic Acid for Noncanonical Target Suppression
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Solution Overview
Problem
Conventional RNA interference materials designed with intact miRNA seed regions inefficiently suppress both canonical and non-canonical target genes, with strong suppression of canonical targets but weak suppression of non-canonical targets.
Innovation Solution
An RNA interference-inducing nucleic acid is developed by modifying a partial sequence of specific miRNA, specifically in positions 2 to 7 from the 5' end, to enhance suppression of non-canonical target genes, using base sequences that allow for G:A or G:U wobble pairs to become canonical base pairs, or substituting guanine with uracil or adenine to improve pairing efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If microRNA is used to inhibit cancer genes, then cancer treatment effectiveness is improved, but off-target effects on noncanonical targets cause harmful side effects
Solution Approach 1:
The patent modifies the microRNA sequence at specific local positions (positions 2-8 or 2-10) to create nucleic acids with altered binding characteristics. These local modifications enable the microRNA to selectively bind to canonical targets while avoiding noncanonical targets, thus resolving the contradiction between treatment effectiveness and off-target effects.
Solution Approach 2:
The patent changes the sequence parameters of the microRNA by introducing specific nucleotide modifications at defined positions. These parameter changes alter the binding affinity and specificity of the microRNA, allowing it to distinguish between canonical and noncanonical targets, thereby reducing harmful off-target effects while maintaining therapeutic effectiveness.
2Ease of operation
If conventional microRNA sequences are used, then treatment simplicity is maintained, but lack of specificity causes unintended inhibition of noncanonical targets
Solution Approach 1:
The patent segments the microRNA sequence into specific regions of interest (positions 2-8 or 2-10) that can be independently modified. This segmentation allows for targeted modifications that enhance specificity without complicating the overall treatment approach, as the modifications are made to discrete, identifiable portions of the sequence.
Solution Approach 2:
The patent introduces modified nucleic acid sequences as intermediaries between the therapeutic intent and the target genes. These modified sequences serve as precise mediators that can selectively inhibit canonical targets while avoiding noncanonical targets, thereby achieving high specificity without sacrificing treatment simplicity.
3Reliability
If microRNA binds to noncanonical targets, then unintended gene inhibition occurs, but distinguishing canonical from noncanonical targets is difficult
Solution Approach 1:
The patent introduces nucleotide modifications that can be detected through sequence analysis, effectively creating a 'color code' that distinguishes canonical from noncanonical targets. By incorporating specific nucleotide changes at positions 2-8 or 2-10, the modified microRNA sequences become detectably different from wild-type sequences, enabling accurate identification and differentiation of target types.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modified RNA interference-inducing nucleic acid selectively and efficiently suppresses non-canonical target genes, achieving stronger biological effects compared to conventional materials by improving the pairing efficiency and specificity.
Implementation Method 1
RNA interference-inducing nucleic acid inhibiting noncanonical targets of micro rna
Implementation Method 2
RNA interference-inducing nucleic acid inhibiting noncanonical targets of micro rna
Data Source
Figure 1
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Figure 2c
AI summary
The present invention relates to RNA interference-inducing nucleic acid that inhibits noncanonical target genes of micro RNA, in which part of the sequence of a specific micro RNA has been modified, and by using the RNA interference-inducing nucleic acid of the present invention, the biological function micro RNA exhibits by inhibiting noncanonical target genes is effectively increased or there is the benefit of selectively exhibiting only one of the biological functions of conventional micro RNA, i.e., the function of inhibiting noncanonical target genes, and the interference-inducing nucleic acid of the present invention enables cell cycling, differentiation, dedifferentiation, formation, movement, splitting, proliferation or death adjustment, and it is expected that the invention can be used in various fields such as drugs and cosmetics.