2′,3′-O Ketal Nucleic Acid Conjugates for Targeted Cell Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing technologies do not effectively deliver nucleic acid molecules, such as siRNA, into target cells with high efficacy.
Innovation Solution
Attaching a 2′,3′—O ketal moiety to the nucleic acid molecule, particularly at the 3′-end and/or 5′-end, enhances the delivery of nucleic acid molecules into target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional nucleic acid molecules are used for delivery, then the basic genetic information can be transmitted, but the delivery efficacy into target cells is insufficient
Solution Approach 1:
The patent creates a composite nucleic acid conjugate by combining nucleic acid molecules with lipid 2′,3′—O ketal moieties. This composite structure leverages the biocompatibility and membrane permeability properties of lipids to enhance the delivery of nucleic acids into target cells, thereby improving both reliability and productivity of delivery.
Solution Approach 2:
The patent modifies the chemical structure of nucleic acid molecules by introducing lipid 2′,3′—O ketal moieties at specific positions (5′-end and/or 3′-end). This structural parameter change transforms the nucleic acid from a poorly membrane-permeable molecule to one with enhanced cellular uptake capabilities, directly addressing the delivery efficacy problem.
2Reliability
If nucleic acid molecules are delivered into cells, then therapeutic or diagnostic effects can be achieved, but the in vivo delivery is not effective
Solution Approach 1:
The patent segments the nucleic acid molecule into distinct regions for modification, specifically targeting the 5′-end and 3′-end positions. By attaching lipid 2′,3′—O ketal moieties at these segmented locations, the invention optimizes cellular uptake while maintaining the integrity of the central nucleic acid sequence, thereby achieving effective in vivo delivery.
Solution Approach 2:
The lipid 2′,3′—O ketal moiety acts as an intermediary bridge between the nucleic acid molecule and the cell membrane. This intermediary structure facilitates the interaction between the hydrophilic nucleic acid and the hydrophobic cell membrane, enabling effective transmembrane delivery in vivo.
3Reliability
If therapeutic nucleic acid molecules are developed, then disease treatment can be achieved, but the delivery vehicle characteristics need improvement
Solution Approach 1:
The patent applies local quality modification by introducing lipid 2′,3′—O ketal moieties only at specific terminal positions (5′-end and/or 3′-end) of the nucleic acid molecule, rather than modifying the entire structure. This localized modification enhances membrane permeability and cellular uptake while preserving the therapeutic functionality of the central nucleic acid sequence, thereby improving therapeutic efficacy without excessive complexity.
Data Source
AI summary
The present invention refers to a nucleic acid conjugate comprising at least one 2′,3′—O ketal moiety. This conjugate is suitable for the target-specific or target-selective delivery of nucleic acid molecules into cells such as mammalian cells including human cells with high efficacy. Thus, a new delivery vehicle for therapeutic nucleic acid molecules including antisense molecules. siRNA molecules, miRNA molecules, antagomirs or precursors of such molecules is provided.