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.
Original patent title: “Genome editing method based on crispr/cas9 system and use thereof”
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. Owned by Chung-Ang University with 15 claims, and it is expected to expire in 2041.
Coverage
What does this patent actually cover?
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 (ClaimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 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.
The gap
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.
- 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.
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
Key facts
What made this novel
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.
The Patent Drawing

Schematic visualization of the patent's claim structure. Hand-drawn diagrams in progress for each landmark patent.
Where you've seen this
Real-world examples
Research labs studying genetic diseases like cystic fibrosis or sickle cell anemia
Companies developing gene therapies for inherited disorders
Agricultural biotechnology for creating disease-resistant crops
Basic science research to understand gene function in cells
Development of transgenic animals for medical research
Why it matters
The bigger picture
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.
Filed
April 2, 2021
Market context
Who's building on this
Companies in this space
Chung-Ang University, the assigneeassigneeThe entity that owns the patent — usually the inventor's employer or a company.Read more →, is actively involved in research in this area. Academic institutions and biotechnology companies worldwide, such as CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics, are continuously exploring methods to enhance CRISPR/Cas9 efficiency and specificity for therapeutic applications. Research groups in agricultural biotechnology are also investigating improved gene editing techniques for crop and livestock modification.
Market impact
This patent contributes to the ongoing effort to refine CRISPR/Cas9 technology, which is a cornerstone of modern genetic engineering. If this method proves significantly more efficient, it could lead to more robust and cost-effective gene therapies and research tools. It could influence the development pipelines of companies working on gene-editing solutions by offering a new strategy to overcome current limitations in editing success rates, potentially accelerating the path to clinical trials and commercial products.
Claim 1 — Plain English
What this patent covers
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.
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.
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.
Patent timeline
Application submitted to the patent office
Patent enters public domain
PatentBrief Score
Impact Score
Limited data
Citation count
0/40
No citations yet
Claim breadth
10/20
Broad claimsclaimsThe numbered statements at the end of a patent that legally define what the inventor owns.Read more →
Recency
0/20
Older than 20 years
Assignee scale
0/20
Independent or smaller assigneeassigneeThe entity that owns the patent — usually the inventor's employer or a company.Read more →
PatentBrief Impact Score — based on citation count, claim breadth, recency, and assignee scale. Not a legal assessment.
Heuristic Value Estimate
What this patent might be worth
$45K – $144K
Midpoint $90K · 14.4 yr remaining · industry ×3.0
Heuristic only — blends forward/backward citation counts, claim scope, time remaining, litigation history, and CPC-derived industry baseline. Real valuations need a professional appraisal.
Claim text not yet imported for this patent
The original legal language
Original claims
15 claims as filed with the patent office.
Concepts involved
Cite this patent
Kim, H. J., LEE, H. J., & Lee, S. J. Improving CRISPR Gene Editing with Intentional DNA Mismatches (U.S. Patent No. 20,240,384,303). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/20240384303/genome-editing-method-based-on-crisprcas9-system-and-use-thereof
Auto-generated from the patent record. Double-check author order and the issue date against the official USPTO document before submitting.
Embed
Add this patent to your site
Drop this plain-English patent card into any blog post or article — free, no signup. It always links back to the full breakdown here.
<div data-patentlens-widget data-patent-number="US20240384303"></div> <script src="https://patentbrief.org/embed.js" async></script>
Stay in the loop
Get a weekly digest of new patents.
One email per week. No spam. Unsubscribe anytime.
Keep exploring
Related patents you should know
US 4683195 · 1987
How to Make Billions of Copies of a DNA Segment
This patent describes the Polymerase Chain Reaction (PCR), a method to rapidly create many copies of a specific piece of DNA or RNA, enabling its detection and analysis.
Cetus Corp
US 8697359 · 2014
How to Edit Genes in Human Cells Using an Engineered CRISPR System
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.
Massachusetts Institute of Technology
US 7657849 · 2010
How the iPhone's Slide-to-Unlock Gesture Works
Apple's 2010 patent describes unlocking a device by dragging a specific graphical image across the touchscreen along a predefined path, a gesture that became iconic with the original iPhone.
Apple Inc
US 4733665 · 1988
How Doctors Implant a Permanent Stent Using a Balloon
This patent describes the method for placing a permanent, expandable wire mesh tube inside a blood vessel or other body tube using a balloon-tipped catheter to widen it and keep it open.
Expandable Grafts Partnership
US 4965188 · 1990
How to Make Many Copies of a DNA Piece with Heat
This patent describes the Polymerase Chain Reaction (PCR) method, a technique to make millions of copies of a specific DNA segment using a heat-resistant enzyme and repeated temperature changes.
Cetus Corp
US 4235871 · 1980
How to Encapsulate Active Materials in Lipid Bubbles Efficiently
This patent describes a method for trapping biologically active substances inside tiny, multi-layered fat bubbles called liposomes, using a specific water-in-oil emulsion and gel-forming process to improve how much material gets captured.
Individual
Semantically similar
You might also find these interesting
US 10113167 · 2018 · Universitaet Wien
How CRISPR-Cas9 Uses RNA to Edit DNA
US 11739322 · 2023 · Institute of Genetics and Developmental Biology of CAS
CRISPR Gene Editing That Turns Itself Off
US 20230383290 · Leland Stanford Junior University
How to Precisely Edit Genes Using Retron-Guide RNA Cassettes
US 8697359 · 2014 · Massachusetts Institute of Technology
How to Edit Genes in Human Cells Using an Engineered CRISPR System
More to explore
More in Biotech & Medicine
US 4683195 · 1987 · Cetus Corp
How to Make Billions of Copies of a DNA Segment
US 8697359 · 2014 · Massachusetts Institute of Technology
How to Edit Genes in Human Cells Using an Engineered CRISPR System
US 4733665 · 1988 · Expandable Grafts Partnership
How Doctors Implant a Permanent Stent Using a Balloon
US 4965188 · 1990 · Cetus Corp
How to Make Many Copies of a DNA Piece with Heat
New to patents?
Common Questions
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.
Patent monitoring





