Beta Helical Protein Conjugates for Direct Cell Membrane Penetration
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Solution Overview
Problem
Current gene therapy methods face challenges in delivering genetic material into cells, particularly for inherited disorders like cystic fibrosis and muscular dystrophy, due to inefficiencies in non-viral approaches and the risk of cancer from viral vectors, and most delivery mechanisms rely on endocytosis-dependent pathways that can lead to drug degradation.
Innovation Solution
A cell-penetrating conjugate comprising a recombinant β helical protein linked to a functional molecule, where the β helical protein has dimensions of 5 nm-25 nm in length and 1 nm-5 nm in width, allowing direct penetration of the cell membrane and avoiding endocytosis, facilitating the delivery of nucleic acids, drugs, and other molecules into cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for gene delivery, then gene transfer efficiency is improved, but risk of cancer induction increases
Solution Approach 1:
The invention segments the gene delivery system into two distinct components: a cell-penetrating peptide (CPP) carrier and the therapeutic nucleic acid cargo. The CPP handles the dangerous membrane penetration function, while the therapeutic payload remains separate until delivery, eliminating the need for viral vectors that integrate genetic material and cause cancer.
Solution Approach 2:
The cell-penetrating peptide acts as an intermediary carrier that facilitates nucleic acid delivery without being a virus. The CPP temporarily binds to the therapeutic cargo, transports it across the cell membrane, and then releases it inside the cell, mediating the delivery process without the harmful integration properties of viral vectors.
2Reliability
If endocytosis-dependent pathways are used for delivery, then cell membrane penetration is achieved, but drug degradation occurs
Solution Approach 1:
Instead of relying on the cell's endocytosis machinery to internalize the drug (which leads to degradation in endosomes/lysosomes), the invention inverts the approach by using a CPP to actively transport the nucleic acid directly through the cell membrane. This reverse strategy avoids the degradative endocytic pathway entirely and delivers the cargo directly to the cytoplasm.
Solution Approach 2:
The invention replaces the biological endocytosis mechanism with a chemically-mediated CPP transport mechanism. The CPP uses its amphipathic structure and membrane-disrupting properties to create a direct translocation pathway, substituting the endocytic route that leads to degradation with a direct membrane-penetration route that preserves cargo integrity.
Data Source
AI summary
A cell penetrating conjugate comprising a recombinant β helical protein linked to a functional molecule wherein the β helical protein length is in the range of from 5 nm to 25 nm, suitably, from 10 nm to 15 nm and width is in the range of from 1 nm to 5 nm, suitably, from 1 nm to 3 nm. Processes for preparing said conjugates and uses thereof are also disclosed.