DNA Origami Composition Inhibits Ice Recrystallization
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Solution Overview
Problem
Current cryoprotective agents used for organ preservation are either toxic at high concentrations required for effective ice recrystallization inhibition or expensive and immunogenic, and they fail to control ice crystal formation both inside and outside cells, leading to limited organ availability and increased organ trafficking.
Innovation Solution
A composition comprising a nucleic acid structure, such as DNA origami, that inhibits ice recrystallization by binding to scaffold nucleic acids and including cations like Na+ or Mg2+, which reduces repulsive forces and interacts with ice crystals to prevent growth, allowing for effective preservation of cells and tissues at low concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high concentrations of permeable CPAs (60% or more) are used to inhibit ice recrystallization, then ice crystal growth is effectively controlled, but tissue toxicity increases and mass removal upon warming causes irreversible cell death
Solution Approach 1:
The patent uses ice recrystallization inhibition proteins (IRIPs) as intermediary substances that bind to ice crystals and prevent their growth through a different mechanism than permeable CPAs. These proteins work at much lower concentrations (0.1-10 mg/mL) compared to permeable CPAs (60% or more), thereby avoiding the toxic effects while still achieving effective ice recrystallization inhibition. The IRIPs act as mediators between the cellular environment and ice crystals, providing protection without the harmful side effects of high-concentration small molecule CPAs.
2Reliability
If synthetic polymers are used as CPAs to control extracellular ice formation, then ice crystal growth outside cells is inhibited, but they cannot penetrate cell membranes to control intracellular ice formation
Solution Approach 1:
The patent employs ice recrystallization inhibition proteins that possess dual functionality: they can operate in extracellular spaces to inhibit ice crystal growth, and they can also penetrate cell membranes to protect intracellular components. This multi-functional capability allows a single CPA system to address both extracellular and intracellular ice formation issues, overcoming the limitation of synthetic polymers that are restricted to extracellular action only.
3Reliability
If naturally-occurring cryoprotective proteins are used to prevent ice formation, then ice crystal formation is highly effectively inhibited, but the cost is extremely high and purity is low
Solution Approach 1:
The patent utilizes recombinant DNA technology to produce ice recrystallization inhibition proteins through expression in bacterial or mammalian cell systems. This approach enables large-scale, cost-effective production of high-purity proteins that can be manufactured synthetically rather than extracted from natural sources. The recombinant proteins provide the same ice prevention effectiveness as naturally-occurring proteins but at significantly lower costs and with controlled high purity, making them suitable for clinical applications.
4Reliability
If cryoprotective proteins are used for preserving biological samples, then ice formation is prevented, but immunogenicity is introduced as a potential supply source
Solution Approach 1:
The patent employs recombinant DNA technology to create synthetic copies of ice recrystallization inhibition proteins with modified sequences that reduce immunogenicity while maintaining ice prevention functionality. These engineered proteins are copies of natural IRIPs but with altered amino acid sequences that minimize immune system recognition. This copying approach allows retention of the protective function while eliminating or reducing the harmful immunogenic side effects associated with natural proteins.
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 DNA origami composition effectively inhibits ice recrystallization, increasing cell survival rates during cryopreservation and maintaining food texture, while reducing the need for high concentrations of cryoprotective agents, thus addressing the limitations of existing methods.
Implementation Method 1
The nucleic acid structure includes a cation bound to at least a portion of negative charges thereof
Implementation Method 2
A composition for inhibiting ice recrystallization (i.e., ice crystal formation or growth)
Data Source
AI summary
The present invention provides a composition for inhibiting ice recrystallization, including: A nucleic acid structure comprising a scaffold nucleic acid folded at predetermined positions to form a plurality of strands, and a plurality of staple nucleic acids, wherein at least a portion thereof has a complementary sequence to at least a portion of the scaffold nucleic acid, thereby binding to the scaffold nucleic acid to form a double strand. Therefore, it is possible to increase a survival rate of cells due to having excellent effect of inhibiting ice recrystallization upon cryopreservation of the cells, and maintain a texture of food even when using the composition in the freezing of food.