Nucleic Acid Compounds with Half-Life Extension Motifs
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Solution Overview
Problem
Delivering therapeutic nucleic acids into cells remains a challenging area of research due to inefficiencies in existing methods, necessitating improved compounds and strategies for nucleic acid introduction.
Innovation Solution
Development of compounds comprising nucleic acids covalently bonded to half-life extension motifs (HLEMs) and uptake motifs (UMs), specifically formulated to enhance cellular uptake, as represented by structures (HLEM)z-A and (HLEM)z-A-(UM)t, where z and t range from 1 to 5, with various linkers and motifs designed to facilitate efficient delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional nucleic acid delivery methods are used, then delivery can be performed with simple methods, but delivery efficiency is low
Solution Approach 1:
The patent applies composite materials by combining nucleic acid with half-life extension motifs (HLEMs) and cellular uptake motifs (CUMs) to create a composite compound. The HLEM contains a cell-penetrating peptide and a half-life extension peptide, while the CUM facilitates cellular internalization. This composite structure resolves the contradiction by enhancing delivery efficiency through multiple functional components while maintaining a systematic approach to complexity management.
Solution Approach 2:
The patent segments the delivery system into distinct functional modules: the nucleic acid payload, the HLEM with its sub-components (cell-penetrating peptide and half-life extension peptide), and the CUM. This segmentation allows each component to perform its specific function independently, improving overall delivery efficiency while making the complex system more manageable and designable.
2Reliability
If nucleic acid is modified with multiple motifs, then cellular uptake and half-life are improved, but compound complexity increases
Solution Approach 1:
The patent implements multi-functionality by designing the HLEM to simultaneously provide half-life extension through the half-life extension peptide and cellular penetration through the cell-penetrating peptide. The CUM additionally provides cellular internalization function. This multi-functional design improves therapeutic delivery reliability by ensuring the compound survives longer in circulation and efficiently enters cells, while the modular nature of these functions helps manage complexity.
3Productivity
If simple nucleic acid compounds are used, then compound structure is simple, but delivery effectiveness is insufficient
Solution Approach 1:
The patent applies preliminary action by pre-constructing the HLEM with its cell-penetrating peptide and half-life extension peptide components before conjugation to the nucleic acid. The CUM is also prepared as a separate module. This preliminary preparation of functional modules simplifies the overall manufacturing process by allowing each component to be optimized and synthesized independently before final assembly, thereby improving delivery effectiveness without excessively complicating the manufacturing workflow.
Data Source
AI summary
Disclosed herein are compounds including a nucleic acid (A), their preparation, and their use.