Engineered Nucleic Acid Guides for Precise Target Hybridization
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Solution Overview
Problem
Existing genome engineering techniques face challenges in achieving precise and specific binding of nucleic acid-targeting nucleic acids to target sequences, leading to non-specific binding and inefficient modification of nucleic acids.
Innovation Solution
Engineered nucleic acid-targeting nucleic acids with mutations in the P-domain or bulge region, allowing for improved hybridization and specificity to target nucleic acids, along with the use of site-directed polypeptides and donor polynucleotides for targeted modification and cleavage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional nucleic acid-targeting nucleic acids are used, then the binding process is simple, but the specificity and precision of binding to target sequences is insufficient
Solution Approach 1:
The patent applies local quality by introducing mutations specifically in the P-domain and bulge region of the nucleic acid-targeting nucleic acid, while maintaining the overall structure and function of the molecule. This localized modification approach improves binding specificity to target sequences without requiring complete redesign of the entire nucleic acid structure, thus resolving the contradiction between binding precision and structural complexity.
2Measurement precision
If mutations are introduced in the P-domain to improve binding specificity, then the precision of target recognition is improved, but the complexity of the nucleic acid structure increases
Solution Approach 1:
The patent applies parameter changes by introducing specific point mutations and modifications in the P-domain and bulge region of the nucleic acid-targeting nucleic acid. These parameter changes (nucleotide substitutions, insertions, or deletions) alter the binding characteristics to achieve higher target recognition precision while maintaining manageable structural complexity through controlled modification rather than complete redesign.
3Productivity
If the nucleic acid-targeting nucleic acid is engineered with specific mutations, then the efficiency of nucleic acid modification is improved, but the difficulty of synthesis and manipulation increases
Solution Approach 1:
The patent applies segmentation by dividing the nucleic acid-targeting nucleic acid into distinct functional regions including the P-domain, bulge region, and other conserved elements. This segmentation allows for targeted engineering of specific regions (such as introducing mutations in the P-domain or bulge region) to improve modification efficiency while keeping the rest of the structure standardized and easy to synthesize using conventional methods.
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
Enhances the specificity and efficiency of nucleic acid modification by reducing non-specific binding and enabling precise genetic manipulation, including insertion and cleavage of target nucleic acids.
Implementation Method 1
the engineered nucleic acid-targeting nucleic acid is adapted to hybridize to a target nucleic acid
Data Source
AI summary
This disclosure provides for compositions and methods for the use of nucleic acid-targeting nucleic acids and complexes thereof. Genome engineering can refer to altering the genome by deleting, inserting, mutating, or substituting specific nucleic acid sequences. The altering can be gene or location specific. Genome engineering can use nucleases to cut a nucleic acid thereby generating a site for the alteration. Engineering of a non-genomic nucleic acid is also contemplated.