snRNA-Based Nucleic Acid Delivery to Cell Nucleus
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Solution Overview
Problem
Current methods for manipulating and inhibiting transcription and splicing complexes face challenges with delivery, stability, toxicity, and specificity, particularly for antisense and siRNA molecules targeting the cell nucleus.
Innovation Solution
A composition comprising an isolated snRNA with a specific Sm site and stem-loop structure, capable of delivering cargo sequences such as antisense oligonucleotides or siRNAs to the nucleus, facilitating gene expression modulation by conjugating nucleic acids to the snRNA for targeted delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense and siRNA molecules are used to target transcription and splicing complexes in the cell nucleus, then gene expression can be modulated, but delivery efficiency and molecular stability are compromised
Solution Approach 1:
The patent uses a modified U6 snRNA molecule as an intermediary carrier to deliver antisense and siRNA molecules to the cell nucleus. This snRNA-based delivery system acts as a mediator that protects the cargo molecules from degradation while facilitating their transport into the nucleus, thereby resolving the contradiction between delivery efficiency and molecular stability
Solution Approach 2:
The invention creates a composite molecular structure by conjugating antisense or siRNA molecules to a modified U6 snRNA backbone. This composite construct combines the stability and nuclear localization capabilities of snRNA with the gene modulation functions of the cargo molecules, achieving both stability and reliability simultaneously
2Productivity
If traditional antisense and siRNA approaches are used for gene manipulation, then gene expression can be inhibited, but delivery to the nucleus and molecular stability are problematic
Solution Approach 1:
The modified U6 snRNA serves as an intermediary delivery vehicle that efficiently transports antisense and siRNA cargo to the cell nucleus. This snRNA-based system overcomes the poor delivery efficiency of traditional approaches by utilizing the natural nuclear import mechanisms of snRNPs (small nuclear ribonucleoproteins)
Solution Approach 2:
The U6 snRNA-based platform provides multi-functionality by simultaneously achieving nuclear localization, protection from degradation, and gene modulation. This universal delivery system can accommodate different types of cargo molecules (antisense, siRNA) while maintaining high delivery efficiency and reliability
3Measurement precision
If nucleic acid cargos are delivered to the nucleus for gene modulation, then specific gene expression can be controlled, but delivery stability and molecular integrity are compromised
Solution Approach 1:
The patent constructs a stable composite molecule by chemically conjugating antisense or siRNA cargo to a modified U6 snRNA backbone. This composite structure protects the labile cargo sequences from nucleases while maintaining their ability to specifically target and modulate gene expression, thereby achieving both precision and stability
Data Source
AI summary
The present invention includes methods for modulating the expression of a gene or mRNA in a cell using small nuclear RNAs comprising specific sequence and structural features and further comprising a nucleic acid cargo.