Branched Polypeptide Carriers with Disulfide Bridges for Nucleic Acid Delivery
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Solution Overview
Problem
Current nucleic acid delivery methods face challenges such as degradation, precipitation, protein binding, low cellular uptake, and poor endosomal escape, leading to inefficient in vivo delivery and cytotoxicity.
Innovation Solution
A branched structure polypeptide carrier with defined amino acid sequences and disulfide bridges is used to form stable nanostructures that electrostatically interact with nucleic acids, enhancing delivery efficiency and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cationic polymers like poly-L-lysine, DEAE-dextran, polyethyleneimine (PEI), and chitosan are used to bind nucleic acids, then nucleic acid protection and cellular internalization are improved, but cytotoxicity increases and nucleic acid expression efficiency decreases
Solution Approach 1:
The patent changes the chemical parameters of the cationic polymer by introducing a specific cyclic structure with controlled molecular weight (500-5000 Da) and defined amino acid sequences. This parameter optimization reduces cytotoxicity while maintaining nucleic acid binding capability and cellular internalization efficiency, resolving the contradiction between protection and harmful effects.
Solution Approach 2:
The patent creates a composite system by combining cyclic polypeptide carriers with nucleic acids in specific stoichiometric ratios (1:1 to 1:10). This composite approach allows the polypeptide to protect and deliver nucleic acids while the controlled composition prevents excessive cytotoxicity, achieving both protection and reduced harm.
2Productivity
If conventional polypeptide carriers are used for nucleic acid delivery, then delivery efficiency is improved, but structural stability and in vivo persistence are insufficient
Solution Approach 1:
The patent segments the polypeptide structure into cyclic configurations with specific amino acid repeats (e.g., (KLLAC)3, (KLLALLAC)3). This segmentation creates a stable cyclic structure that resists proteolytic degradation while maintaining delivery functionality, thereby improving both structural stability and in vivo persistence without sacrificing delivery efficiency.
Solution Approach 2:
The patent uses partial cyclization of polypeptide chains to create stable cyclic structures that persist in vivo. By controlling the degree of cyclization and molecular weight (500-5000 Da), the patent achieves sufficient structural stability and in vivo persistence while maintaining adequate delivery efficiency, avoiding excessive structural rigidity that would harm delivery.
3Ease of manufacture
If linear polypeptide structures are used, then synthesis simplicity is maintained, but binding affinity and stability are reduced
Solution Approach 1:
The patent segments the polypeptide into modular cyclic units with specific amino acid sequences (e.g., KLLAC repeats). This modular cyclic structure can be synthesized through standardized protocols while achieving superior binding affinity and stability compared to linear structures, resolving the contradiction between synthesis simplicity and structural reliability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The branched polypeptide carrier achieves high gene delivery efficiency, structural stability, and low toxicity, enabling targeted nucleic acid delivery to tissues and organs in vivo.
Implementation Method 1
Cationic compounds can electrostatically bind with nucleic acids, compressing and protecting them from enzymatic degradation
Implementation Method 2
The branched structure polypeptide contains at least one disulfide bridge
Data Source
AI summary
The disclosure provides a branched structure polypeptide peptide carrier and its variations. The branched structure peptide has the following sequence formula:The technical solution of the disclosure enables efficient delivery of nucleic acids to tissues and organs in vivo for targeted therapy. The polypeptides have several times more conformational flexibility and affinity than macromolecular drugs (proteins and antibodies). The branched structure polypeptides possess long-lasting in vivo stability while maintaining strong affinity and minimal toxicity. By forming stable nanocomplexes or nanoparticles through electrostatic interactions with nucleic acid molecules, they can facilitate the delivery of nucleic acid drugs and their stable release inside cells, thereby enhancing the activity of nucleic acid-based therapeutics.