Macromolecule Transduction Domain Peptides for Cell Permeability
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Solution Overview
Problem
Current delivery systems for macromolecules like DNA, RNA, proteins, and peptides face challenges such as poor penetration into tissues or cells, toxicity due to non-specific targeting, and degradation, leading to inadequate delivery and side effects.
Innovation Solution
Development of novel macromolecule transduction domain (MTD) peptides with a specific amino acid sequence (SEQ ID NO: 173) that facilitate the transport of biologically active molecules across cell membranes, enabling efficient delivery through cell permeability and minimizing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional delivery systems are used to deliver macromolecules, then delivery can be achieved, but penetration into tissue or cell is poor
Solution Approach 1:
The patent uses cell-penetrating peptides (CPPs) as intermediary carriers to facilitate the transport of macromolecules across the plasma membrane. These peptides act as mediators that enable the delivery of cargo molecules (proteins, peptides, oligonucleotides) that would otherwise be unable to penetrate the membrane, thereby resolving the contradiction between delivery reliability and penetration capability
Solution Approach 2:
The invention creates composite structures by fusing cargo molecules with cell-penetrating peptide sequences. This composite approach combines the membrane-penetration capability of CPPs with the therapeutic function of the cargo, enabling both penetration and reliable delivery of macromolecules to target cells
2Quantity of substance
If high concentration is used to achieve adequate local concentration at target, then delivery amount increases, but toxicity and side effects increase
Solution Approach 1:
The patent employs cell-penetrating peptides with specific sequences (such as penetratin, Tat peptide, transportan, VP22) that provide targeted cell penetration capability. This allows the delivery system to concentrate the therapeutic effect locally at the target cell membrane and interior, while minimizing exposure and toxic effects in non-target tissues, thereby achieving adequate local concentration without proportional increase in systemic toxicity
3Quantity of substance
If macromolecules are delivered systemically, then delivery coverage increases, but non-specific targeting causes toxicity
Solution Approach 1:
The cell-penetrating peptides serve as selective intermediaries that facilitate macromolecule delivery specifically at target cells. The peptides' ability to interact with cell membranes and facilitate internalization provides a degree of targeting specificity, reducing non-specific uptake in non-target tissues and thereby minimizing toxicity while maintaining broad delivery coverage
4Productivity
If currently known delivery systems are used, then some cellular uptake can be achieved, but efficiency is limited and toxicity remains
Solution Approach 1:
The patent systematically varies parameters of the cell-penetrating peptide sequences (amino acid composition, length, charge distribution, hydrophobicity) to optimize both cellular uptake efficiency and reduce toxicity. By adjusting these parameters, the invention achieves enhanced productivity in macromolecule delivery while minimizing harmful effects through rational peptide design
Data Source
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AI summary
The present invention discloses novel macromolecule transduction domain (MTD) peptides which facilitate the traverse of a biologically active molecule across the cell membrane. Also disclosed are polynucleotides encoding the MTD peptides, methods of identifying the MTD peptides; methods of genetically engineering a biologically active molecule to have cell permeability by using the MTD peptides, methods of importing a biologically active molecule into a cell by using the MTD peptides, and uses thereof.