# Improving CRISPR Gene Editing with Intentional DNA Mismatches > This patent describes a method to make CRISPR/Cas9 gene editing more effective by intentionally creating small mismatches between the guide RNA and the target DNA sequence. - **Patent:** US 20240384303 - **Original title:** Genome editing method based on crispr/cas9 system and use thereof - **Owner:** Chung-Ang University - **Status:** Active - **Times cited:** 0 - **Field:** biotech, pharmaceutical, gene_editing, biotechnology ## What it does This patent details a genome editing method using the CRISPR/Cas9 system that includes a 'donor nucleic acid molecule' and 'guide RNA'. The core idea is to intentionally create 'one or more mismatched nucleotides' between the target DNA and the guide RNA sequence (Claim 1). This mismatch is designed to increase the efficiency of genome editing (Claim 8). The guide RNA can be a single-chain guide RNA (sgRNA) or a dual RNA (crRNA and tracrRNA) (Claim 2). The donor nucleic acid molecule then causes specific genetic changes, such as substituting, inserting, or deleting nucleotides, or even knocking out or knocking in entire sequences (Claim 5, 6). For example, to correct a specific genetic mutation, a guide RNA with a planned mismatch would direct the Cas9 enzyme to the target DNA, and a donor nucleic acid would provide the correct sequence to be inserted. ## What it does NOT cover - Does not cover CRISPR/Cas9 genome editing methods that do not involve generating one or more mismatched nucleotides between the target DNA and the guide RNA. - Does not cover gene editing systems that do not rely on the CRISPR/Cas9 mechanism, such as zinc finger nucleases or TALENs. - Does not cover methods where the guide RNA perfectly matches the target DNA sequence without any intentional mismatches. - Does not cover simply delivering CRISPR/Cas9 components to a cell without the specific mismatch strategy described. - Does not cover modifications to the Cas9 enzyme itself to improve specificity or reduce off-target effects, unless those modifications are used in conjunction with the mismatch strategy. ## The clever bit The clever bit is intentionally introducing a mismatch between the guide RNA and the target DNA. Instead of aiming for a perfect match, which is the standard approach, this method uses a slight mismatch to surprisingly improve the editing process, specifically by increasing the efficiency of the CRISPR/Cas9 system. ## Real-world examples 1. Research labs studying genetic diseases like cystic fibrosis or sickle cell anemia 2. Companies developing gene therapies for inherited disorders 3. Agricultural biotechnology for creating disease-resistant crops 4. Basic science research to understand gene function in cells 5. Development of transgenic animals for medical research ## Why it matters CRISPR/Cas9 is a powerful tool for gene editing, but its efficiency can vary. This patent aims to improve that efficiency, making it more reliable for research and therapeutic applications. Higher efficiency means a greater chance of successfully making the desired genetic change, which is crucial for developing treatments for genetic diseases or creating improved crops. This could reduce the amount of material needed or the number of attempts required to achieve a specific edit. ## Frequently asked questions ### What does Improving CRISPR Gene Editing with Intentional DNA Mismatches cover? This patent describes a method to make CRISPR/Cas9 gene editing more effective by intentionally creating small mismatches between the guide RNA and the target DNA sequence. ### Who owns patent US 20240384303? This patent is owned by Chung-Ang University. ### When does this patent expire? This patent is expected to expire on April 2, 2041, when the invention enters the public domain. ### What problem does this patent solve? CRISPR/Cas9 is a powerful tool for gene editing, but its efficiency can vary. This patent aims to improve that efficiency, making it more reliable for research and therapeutic applications. Higher efficiency means a greater chance of successfully making the desired genetic change, which is crucial for developing treatments for genetic diseases or creating improved crops. This could reduce the amount of material needed or the number of attempts required to achieve a specific edit. ### What does this patent NOT cover? Does not cover CRISPR/Cas9 genome editing methods that do not involve generating one or more mismatched nucleotides between the target DNA and the guide RNA. **Full plain-English explainer:** https://patentbrief.org/patent/us/20240384303/genome-editing-method-based-on-crisprcas9-system-and-use-thereof **Original patent:** https://patents.google.com/patent/US20240384303 --- _Source: PatentBrief — https://patentbrief.org. Patent facts are from public records; the plain-English explanation is PatentBrief's._ ## Related patents Semantically similar inventions in the PatentBrief corpus: - [How CRISPR-Cas9 Uses RNA to Edit DNA](https://patentbrief.org/patent/us/10113167/methods-and-compositions-for-rna-directed-target-dna-modification-and-for-rna-directed-modulation-of-transcription) — This patent describes the fundamental mechanism of using a two-part RNA system to guide the Cas9 protein to specific locations in DNA for precise editing. - [CRISPR Gene Editing That Turns Itself Off](https://patentbrief.org/patent/us/11739322/method-for-genome-editing-using-a-self-inactivating-crispr-nuclease) — This patent describes a CRISPR gene editing system that turns itself off after making a specific genetic change, using a second guide RNA to inactivate the editing enzyme. - [How to Precisely Edit Genes Using Retron-Guide RNA Cassettes](https://patentbrief.org/patent/us/20230383290/high-throughput-precision-genome-editing) — This patent describes a method for highly efficient and precise genome editing using a retron-guide RNA cassette to deliver large pieces of donor DNA into a cell's genetic material. - [How to Edit Genes in Human Cells Using an Engineered CRISPR System](https://patentbrief.org/patent/us/8697359/crispr-gene-editing) — This patent describes an engineered CRISPR-Cas9 system for precisely cutting DNA in eukaryotic cells to change how genes work, opening the door for gene editing in complex organisms. - [How to Use Many CRISPR Guides to Study Many Genes at Once](https://patentbrief.org/patent/us/20180305704/crispr-cas-component-systems-methods-and-compositions-for-sequence-manipulation) — This patent describes a method to use a large collection of CRISPR-Cas9 guide RNAs to target and modify many different genes or DNA regions across a population of eukaryotic cells, enabling high-throughput genetic screening.