Modified miRNA Backbone Structure for Exosomal Small RNA Expression
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Solution Overview
Problem
Current small RNA expression methods, particularly using miR backbones, suffer from low expression quantity and poor therapeutic effects due to instability and unsatisfactory expression levels in cells and exosomes, limiting their application in disease treatment.
Innovation Solution
A modified nucleic acid molecule with a 5'-3' structure comprising specific flanking and Loop sequences, along with a compensatory sequence, is used to enhance the expression of small RNA molecules, forming a stem-loop structure that increases intracellular and exosomal expression levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If current miR backbone structures are used for small RNA expression, then the RNA can be expressed in cells, but the expression quantity is low and the RNA is unstable
Solution Approach 1:
The patent modifies the miR backbone structure by changing specific sequence parameters - removing the AATTCG sequence from the 5' flanking region and the CACCGGT sequence from the 3' flanking region, and optimizing the Loop sequence. These parameter changes in the nucleic acid sequence improve both the stability and expression quantity of the small RNA molecules.
2Reliability
If small RNA is delivered to target organs, then therapeutic effects can be achieved, but the delivery efficiency is insufficient with current methods
Solution Approach 1:
The patent utilizes exosomes as intermediary carriers to deliver small RNA molecules to target organs. The optimized miR backbone structure enables efficient loading of small RNA into exosomes, which then serve as protective vehicles for transport through the bloodstream to target tissues, significantly improving delivery efficiency while maintaining therapeutic effects.
Data Source
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AI summary
Provided are a nucleic acid molecule and a use thereof. The nucleic acid molecule comprises a miRNA backbone nucleic acid molecule for generating a target small molecule RNA. Also provided is an expression vector comprising the nucleic acid molecule. When the miRNA backbone nucleic acid molecule and the expression vector are used for expression of a target small molecule RNA, the expression quantity of the target small molecule RNA in a host cell and the expression quantity of the target small molecule RNA in exosomes secreted by the host cell can be increased.