Modified Cry Protein Crystals for Intracellular Therapeutic Delivery
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Solution Overview
Problem
Effective delivery of therapeutic proteins to targeted tissues or organs remains a major obstacle due to variations in specific routes, protein stability, and bioavailability, hindering desired therapeutic outcomes.
Innovation Solution
Development of modified Cry proteins with specific amino acid modifications that form crystals upon expression, enabling them to act as cell-penetrating peptides, facilitating the delivery of therapeutic proteins into target cells by forming crystals that are efficiently taken up by macropinocytosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic proteins are administered to patients, then treatment of life-threatening illnesses is enabled, but effective delivery to targeted tissue or organ site remains a major obstacle
Solution Approach 1:
The patent uses modified Cry proteins as intermediary carriers to deliver therapeutic proteins to target cells. The Cry protein acts as a mediator that facilitates cellular uptake through crystal formation and macropinocytosis, solving the delivery obstacle without requiring complex external delivery systems
Solution Approach 2:
The patent modifies the Cry protein by changing specific amino acid residues (e.g., replacing residues with charged residues like lysine or arginine) to enhance its cell-penetrating capability. These parameter changes in the protein structure enable effective delivery while maintaining simplicity
2Productivity
If modified Cry proteins are used to deliver therapeutic proteins, then delivery efficiency is enhanced, but protein stability and bioavailability vary dramatically
Solution Approach 1:
The patent creates a composite system where the modified Cry protein forms a crystal structure that encapsulates and protects the therapeutic protein. This composite approach enhances both delivery efficiency and protein stability by combining the cell-penetrating properties of Cry with the therapeutic payload
Solution Approach 2:
The therapeutic delivery system is segmented into distinct functional components: the modified Cry protein carrier, the crystal structure for protection, and the therapeutic protein payload. This segmentation allows each component to optimize its function while working together
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 modified Cry proteins effectively transport therapeutic proteins into mammalian cells, enhancing delivery efficiency and biological activity, as demonstrated by the intracellular delivery of proteins like p53 and p16, leading to cellular effects such as G1 cell cycle arrest and apoptosis.
Implementation Method 1
the polypeptide forms crystal upon being expressed in a host cell
Implementation Method 2
facilitating the delivery of therapeutic proteins into target cells by forming crystals that are efficiently taken up by macropinocytosis
Data Source
AI summary
Provided are novel recombinant proteins that are capable of self-crystallization and exhibit desirable physical properties such as enhanced cellular uptake or and endoso-mal escape. Polynucleotides encoding the recombinant proteins as well as methods of making and using such proteins are also described.