Molecular Guide System Peptide Conjugates for Intracellular Delivery
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Solution Overview
Problem
Therapeutic monoclonal antibodies (MAbs) are limited to extracellular and cell surface targets due to their inability to penetrate cells, missing the opportunity to modulate intracellular protein-protein interactions, which are crucial for treating life-threatening diseases like cancer and infectious diseases.
Innovation Solution
Development of molecular guidance system (MGS) peptides that conjugate with antibodies to facilitate intracellular delivery, targeting specific cell compartments such as the lysosome, Golgi apparatus, endoplasmic reticulum, or nucleus, enabling intracellular therapeutic strategies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic monoclonal antibodies are used, then the ability to modulate protein-protein interactions is improved, but the ability to penetrate cells and reach intracellular targets deteriorates
Solution Approach 1:
The patent combines therapeutic monoclonal antibodies with cell-penetrating peptides to create a hybrid molecule that merges the protein-protein interaction modulation capability of antibodies with the cell penetration capability of peptides. This allows the conjugate to both enter cells and modulate intracellular protein-protein interactions.
Solution Approach 2:
The cell-penetrating peptide acts as an intermediary that facilitates the entry of the antibody into the cell. The peptide conjugate serves as a mediator that enables the antibody to overcome its natural impermeability to cell membranes while retaining its therapeutic function.
2Stability of the object's composition
If antibodies are limited to extracellular targets, then cell permeability is maintained (as they are not cell permeable), but the therapeutic potential for intracellular targets deteriorates
Solution Approach 1:
The patent changes the permeability parameter of the antibody by conjugating it with cell-penetrating peptides. This modification transforms the antibody from being impermeable to cells to being capable of entering cells, thereby expanding its therapeutic applications to intracellular targets.
Solution Approach 2:
The conjugated antibody-peptide complex achieves multi-functionality: it retains the antibody's ability to modulate protein-protein interactions while gaining the ability to penetrate cell membranes and reach intracellular targets, thus expanding its therapeutic scope.
Data Source
AI summary
Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.