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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.

ActiveExpires 2041Owned by Chung-Ang UniversityInvented by Hyun Ju Kim, Ho Joung LEE, Sang Jun Lee

Original patent title: “Genome editing method based on crispr/cas9 system and use thereof”

Plain-English explanation by SahiLast reviewed · October 27, 2026

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

Patent numberUS 20240384303
StatusActive
FieldBiotech & Medicine
AssigneeChung-Ang University
InventorsHyun Ju Kim, Ho Joung LEE, Sang Jun Lee
Filed2021
Expires2041
Claims15
Times cited0
LitigationNone on record
Value · $45K–$144KMinimal

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

Representative patent drawing for Genome editing method based on crispr/cas9 system and use thereof (US 20240384303)
Representative figure · US 20240384303All figures on Google Patents →
Genome editing method based on…(Primary claim)biotechpharmaceuticalgene editingbiotechnology

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

01

Research labs studying genetic diseases like cystic fibrosis or sickle cell anemia

02

Companies developing gene therapies for inherited disorders

03

Agricultural biotechnology for creating disease-resistant crops

04

Basic science research to understand gene function in cells

05

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

Filing

Application submitted to the patent office

Expiration

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

Minimal

$45K – $144K

Midpoint $90K · 14.4 yr remaining · industry ×3.0

Adjust inputs →

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

ClaimPrior artNon-obviousnessNoveltySpecificationAssigneePatent term

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.

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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.

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Last reviewed: October 27, 2026 · PatentBrief is not a law firm and this is not legal advice.