How CRISPR Nickases Precisely Edit Genes in Human Cells
This patent describes an engineered CRISPR-Cas system that uses a modified Cas9 protein, called a nickase, to cut only one strand of DNA in a eukaryotic cell, enabling more precise gene editing or altering gene expression.
Original patent title: “CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes”
This patent describes an engineered CRISPR-Cas system that uses a modified Cas9 protein, called a nickase, to cut only one strand of DNA in a eukaryotic cell, enabling more precise gene editing or altering gene expression. Owned by Massachusetts Institute of Technology with 33 claims and 268 forward citations, and it is expected to expire in 2034.
Coverage
What does this patent actually cover?
This patent details a method for altering gene expression or editing the genome within a eukaryotic cell, like a human cell. It involves introducing an engineered CRISPR-Cas system that includes a guide RNA and a special Type-II Cas9 protein. Crucially, this Cas9 protein has specific mutations in its cutting part, called the catalytic domain, turning it into a 'nickase' that only cleaves one strand of the DNA molecule (ClaimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1). The system also includes at least two nuclear localization signals (NLSs) to ensure it gets into the cell's nucleus where the DNA is located. This single-strand cut can then be repaired by the cell, often with the help of a provided homologous recombination (HR) template, allowing for precise changes to the DNA sequence (Claim 2, 15). For example, this could be used to correct a single faulty letter in a gene that causes a genetic disease.
The gap
What does this patent NOT cover?
- Does not cover CRISPR-Cas systems that create double-strand breaks in DNA, as this system specifically uses a nickase to cleave only one strand.
- Does not cover gene editing or expression alteration in prokaryotic cells, as the claimsclaimsThe numbered statements at the end of a patent that legally define what the inventor owns.Read more → specify a 'eukaryotic cell'.
- Does not cover naturally occurring CRISPR-Cas systems, as the claimsclaimsThe numbered statements at the end of a patent that legally define what the inventor owns.Read more → require an 'engineered, non-naturally occurring' system.
- Does not cover Cas9 proteins that lack specific mutations in their catalytic domain, which are necessary to make it a nickase.
- Does not cover CRISPR-Cas systems that do not include at least two nuclear localization signals (NLSs).
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
Key facts
What made this novel
The cleverness lies in modifying the Cas9 protein to become a 'nickase' that only cuts one strand of DNA. This single-strand break is less damaging to the cell than a double-strand break and can be precisely repaired using a template, allowing for highly accurate gene editing with fewer unintended changes.
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
Gene therapy research for genetic disorders like cystic fibrosis or sickle cell anemia
Developing disease models in cell lines for drug discovery
Basic research to understand gene function in mammalian cells
Precision genome editing for correcting single-nucleotide mutations
Base editing technologies that build upon nickase capabilities
Why it matters
The bigger picture
CRISPR nickases are a vital tool in gene editing because they offer a safer, more precise way to modify DNA compared to traditional Cas9, which creates double-strand breaks. Double-strand breaks can sometimes lead to unwanted, large-scale deletions or insertions in the genome. By only cutting one strand, nickases significantly reduce these off-target effects and enable high-fidelity homology-directed repair, which is crucial for therapeutic applications aiming to correct specific genetic mutations.
Filed
April 22, 2014
Market context
Who's building on this
Companies in this space
The Massachusetts Institute of Technology, through its Broad Institute, continues to be a leader in CRISPR technology development. Companies like Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics, all pioneers in CRISPR-based therapies, are actively building on and refining gene editing tools, including those that leverage the precision of nickases. Beam Therapeutics, for instance, focuses on base editing, which often utilizes nickases for highly targeted single-letter DNA changes.
Market impact
This patent, part of the broader CRISPR-Cas intellectual property landscape, has significantly influenced the gene editing market by enabling more precise and safer genomic modifications. The development of nickase systems has reduced concerns about off-target effects and large chromosomal rearrangements, making CRISPR a more viable tool for therapeutic applications. This precision has spurred investment in gene therapy companies and broadened the scope of genetic diseases considered treatable, moving the field closer to clinical realities.
Claim 1 — Plain English
What this patent covers
This patent details a method for altering gene expression or editing the genome within a eukaryotic cell, like a human cell. It involves introducing an engineered CRISPR-Cas system that includes a guide RNA and a special Type-II Cas9 protein. Crucially, this Cas9 protein has specific mutations in its cutting part, called the catalytic domain, turning it into a 'nickase' that only cleaves one strand of the DNA molecule (Claim 1). The system also includes at least two nuclear localization signals (NLSs) to ensure it gets into the cell's nucleus where the DNA is located. This single-strand cut can then be repaired by the cell, often with the help of a provided homologous recombination (HR) template, allowing for precise changes to the DNA sequence (Claim 2, 15). For example, this could be used to correct a single faulty letter in a gene that causes a genetic disease.
The clever bit
The cleverness lies in modifying the Cas9 protein to become a 'nickase' that only cuts one strand of DNA. This single-strand break is less damaging to the cell than a double-strand break and can be precisely repaired using a template, allowing for highly accurate gene editing with fewer unintended changes.
What it does not cover
- Does not cover CRISPR-Cas systems that create double-strand breaks in DNA, as this system specifically uses a nickase to cleave only one strand.
- Does not cover gene editing or expression alteration in prokaryotic cells, as the claims specify a 'eukaryotic cell'.
- Does not cover naturally occurring CRISPR-Cas systems, as the claims require an 'engineered, non-naturally occurring' system.
- Does not cover Cas9 proteins that lack specific mutations in their catalytic domain, which are necessary to make it a nickase.
- Does not cover CRISPR-Cas systems that do not include at least two nuclear localization signals (NLSs).
Patent timeline
Application submitted to the patent office
Patent enters public domain
PatentBrief Score
Impact Score
High impact
Citation count
40/40
Highly cited
Claim breadth
20/20
Very broad protection
Recency
0/20
Older than 20 years
Assignee scale
20/20
Major company or institution
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
$1.2M – $3.8M
Midpoint $2.4M · 7.5 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
33 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Cong, L., & Zhang, F. How CRISPR Nickases Precisely Edit Genes in Human Cells (U.S. Patent No. 20,140,248,702). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/20140248702/crispr-cas-nickase-systems-methods-and-compositions-for-sequence-manipulation-in
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 How CRISPR Nickases Precisely Edit Genes in Human Cells cover?
This patent describes an engineered CRISPR-Cas system that uses a modified Cas9 protein, called a nickase, to cut only one strand of DNA in a eukaryotic cell, enabling more precise gene editing or altering gene expression.
Who owns patent US 20140248702?
This patent is owned by Massachusetts Institute of Technology.
When does this patent expire?
This patent is expected to expire on April 22, 2034, when the invention enters the public domain.
What is patent US 20140248702 cited by?
This patent has been cited by 268 later patents that build on its ideas.
What problem does this patent solve?
CRISPR nickases are a vital tool in gene editing because they offer a safer, more precise way to modify DNA compared to traditional Cas9, which creates double-strand breaks. Double-strand breaks can sometimes lead to unwanted, large-scale deletions or insertions in the genome. By only cutting one strand, nickases significantly reduce these off-target effects and enable high-fidelity homology-directed repair, which is crucial for therapeutic applications aiming to correct specific genetic mutations.
What does this patent NOT cover?
Does not cover CRISPR-Cas systems that create double-strand breaks in DNA, as this system specifically uses a nickase to cleave only one strand.
Same assignee
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