Rotationally Sequestered Translators for Nucleic Acid Logic
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Solution Overview
Problem
Current nucleic acid-based computing approaches, such as toe-hold sequestering and toe-hold exchange, face limitations including slow information propagation, toxicity due to long single-stranded regions, and signal leak issues, which hinder their effectiveness in biological environments.
Innovation Solution
The development of rotationally sequestered translators with specific nucleic acid complexes and chemical modifications that prevent toe-hold clashing, allowing for high-yield and fast strand displacement reactions while minimizing toxicity and signal leak, using dual toe-holds and chemically modified nucleic acid fragments to control binding interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If toe-hold sequestering is used to enable conditional availability of nucleic acid sequences, then translators can be constructed for logic operations, but information propagation becomes slow and toxicity increases due to long single-stranded regions
Solution Approach 1:
The nucleic acid strands are divided into multiple fragments (first fragment, second fragment, third fragment) that can be independently configured. This segmentation allows the single-stranded regions to be minimized while maintaining the necessary conditional availability functionality through the duplex region formations between specific fragments.
Solution Approach 2:
Different regions of the nucleic acid complexes are given different properties: the duplex regions provide stable binding for conditional availability, while the single-stranded fragments are minimized to reduce toxicity and improve speed. The local configuration of each fragment varies to optimize both functionality and performance.
2Adaptability or versatility
If long single-stranded regions are present in nucleic acid complexes, then binding flexibility is increased, but toxicity increases and background reactivity occurs
Solution Approach 1:
Instead of using long single-stranded regions for binding flexibility, the invention uses partial duplex formations between specific fragments (first fragment with first fragment, second fragment with second fragment, etc.) to achieve the necessary binding flexibility. This partial action approach provides sufficient binding capability while minimizing the harmful effects of long single-stranded regions.
3Productivity
If conventional nucleic acid complexes are used for strand displacement reactions, then basic translation is achieved, but signal leak occurs and yield is incomplete
Solution Approach 1:
The nucleic acid complexes are designed with asymmetric fragment configurations where specific fragments (first, second, third fragments) are positioned to form duplex regions with complementary strands. This asymmetric arrangement creates directional strand displacement reactions that proceed with high yield while preventing signal leak through the specific geometry of the duplex formations.
4Speed
If multiple duplex regions are formed in nucleic acid complexes, then translation speed is improved, but device complexity increases
Solution Approach 1:
Multiple duplex regions are merged into a single integrated nucleic acid complex structure where the first, second, and third fragments are arranged to form multiple duplex regions simultaneously. This merging approach allows high translation speed through multiple concurrent binding events while avoiding the complexity of separate, modular components by using a unified complex design.
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
This approach enables complete yield and significantly improved translation speed, reducing background reactivity and toxicity, and maintaining reactivity across a wide dynamic range of concentrations, making it suitable for biological applications.
Implementation Method 1
Hybridization involves free, single-stranded stretches of nucleic acids. Accordingly, a nucleic-acid network may be regulated by the availability of these free strands.
Data Source
AI summary
Provided are nucleic acid translators capable of carrying out logic operations with improved efficiency, maximized output and reduced off-target effects, in particular in a biological system. Methods of using these translators to transduce signal are also provided.