Cyclic Peptide Vehicles for Endosomal Escape and Cell Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing nucleic acid-based therapeutic agents face challenges in efficiently gaining access to intracellular compartments when administered systemically, with current carrier systems like polymers and cationic liposomes exhibiting low intracellular delivery efficiency.
Innovation Solution
Development of cyclic peptides, specifically endosomal escape vehicles (EEVs) comprising cell penetrating peptides (CPPs) conjugated with exocyclic peptides (EPs) that facilitate intracellular delivery of therapeutic molecules by forming cyclic structures through peptide bonds or linkers, utilizing non-natural amino acids and nuclear localization signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If carrier systems such as polymers or cationic liposomes are used to facilitate intracellular delivery, then delivery capability is improved, but intracellular delivery efficiency remains low
Solution Approach 1:
The patent modifies the chemical structure of peptides by incorporating non-natural amino acids with specific side chains (aromatic, heteroaromatic, guanidine-containing, or basic) to change the physicochemical parameters of the delivery vehicle, enabling efficient intracellular delivery while maintaining stability
Solution Approach 2:
The invention creates composite cyclic peptide structures combining multiple functional elements: cell penetrating peptides, exocyclic peptides with nuclear localization signals, and non-natural amino acid residues, achieving synergistic effects for improved delivery efficiency
2Reliability
If cyclic peptides with non-natural amino acids are synthesized through multi-step procedures, then delivery efficiency is improved, but synthesis complexity increases
Solution Approach 1:
The patent divides the cyclic peptide into distinct functional segments: cell penetrating peptide portion, exocyclic peptide portion with nuclear localization signals, and linker regions, allowing independent optimization and simplified synthesis of each module
Solution Approach 2:
The cyclic peptide structure is designed to perform multiple functions simultaneously: cellular membrane penetration, endosomal escape, and nuclear targeting through integrated motifs, reducing the need for separate delivery vehicles and simplifying overall synthesis
3Ease of manufacture
If conventional peptide synthesis methods are used, then manufacturing simplicity is maintained, but delivery efficacy to intracellular compartments is insufficient
Solution Approach 1:
The patent modifies peptide parameters by incorporating non-natural amino acids with specific functional side chains that enhance cellular uptake and intracellular delivery, achieving superior efficacy while maintaining conventional synthesis methodologies
Data Source
AI summary
The present disclosure relates to the synthesis of cyclic peptides that are able to effectively deliver cargo, e.g., a therapeutic moiety (TM), inside a cell to treat a variety of conditions and diseases.