Base Editor Cancer Mutation Evaluation System
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Solution Overview
Problem
Current methods for evaluating cancer mutations are limited in determining causal relationships and inducing mutations across the genome, failing to accurately assess the effect of specific mutations on cancer development and cell proliferation.
Innovation Solution
A method using guide RNAs and base editors to introduce and evaluate approximately 30,000 to 100,000 single nucleotide cancer mutations in cells, allowing for the classification of mutation functions based on their effect on cell proliferation, and identifying mutations resistant to anticancer drugs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If statistical methods are used to identify cancer mutations, then the frequency of mutations can be found, but the causal relationship between mutations and tumorigenesis cannot be determined
Solution Approach 1:
The patent introduces base editors as an intermediary tool that enables direct functional validation of mutations in cellular models. This mediator bridges the gap between statistical association and causal determination by allowing precise introduction of candidate mutations and observation of their functional effects on cell proliferation and tumorigenesis.
Solution Approach 2:
The patent replaces traditional statistical analysis methods with a functional biology approach using base editing technology. This substitution transitions from passive observation of mutation frequencies to active experimentation where mutations are precisely introduced and their causal effects on cancer development are directly measured through cellular assays.
2Productivity
If existing gene editing techniques are used, then some mutations can be induced, but large-scale induction of various mutations throughout the genome is impossible
Solution Approach 1:
The patent employs base editors with universal applicability across the genome. The base editor system can be programmed with different guide RNAs to target any genomic location, enabling induction of various types of point mutations (C>T, A>G) throughout the entire genome, thus achieving both high productivity and comprehensive genome-wide coverage.
Solution Approach 2:
The patent utilizes the ability to change editing parameters by selecting different base editor variants (e.g., CBE for C>T conversions, ABE for A>G conversions) and adjusting guide RNA sequences to target specific genomic locations. This parameter flexibility enables systematic induction of diverse mutations across the genome at high throughput.
3Productivity
If base editors are used to evaluate cancer mutations, then the function of about 100,000 cancer mutations can be evaluated at once, but the complexity of the evaluation system increases
Solution Approach 1:
The patent segments the complex evaluation process into distinct modular components: base editor construction modules, guide RNA design modules, cellular transfection modules, and data analysis modules. Each module can be independently optimized and validated, reducing overall system complexity while maintaining high-throughput capability for evaluating 100,000+ mutations.
Solution Approach 2:
The patent uses standardized protocols and reusable base editor constructs that can be copied and applied across thousands of mutation evaluation experiments. The guide RNA sequences and base editor plasmids serve as templates that can be replicated and used in high-throughput formats, reducing the complexity burden of evaluating large numbers of mutations.
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
Enables accurate evaluation of cancer mutation functions at a single nucleotide level, effectively extracting relevant mutations from databases and discovering drug-resistant mutations, thereby advancing cancer research and treatment.
Implementation Method 1
Cytosine base editors are constructed by fusing a naturally-derived cytosine deaminase to dCas9 or nCas9, and are able to convert cytosine to thymine without cutting the gene or inserting an additional donor DNA
Implementation Method 2
adenine base editors are constructed by fusing an artificially modified adenosine deaminase with a Cas9 variant, and are known to be capable of converting adenine to guanine
Data Source
AI summary
The disclosure relates to a method of evaluating functions of cancer mutations using base editors and guide RNAs, an evaluation system for mutations, and a computer-readable recording medium in which is recorded a program for executing the method by a computer.