How to Make Animals That Can Turn On CRISPR Gene Editing
This patent describes creating genetically modified non-human animals, like mice, where a key CRISPR gene-editing protein (Cas9) can be turned on only in specific cells or at specific times using a special genetic switch.
Original patent title: “Delivery, Engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications”
This patent describes creating genetically modified non-human animals, like mice, where a key CRISPR gene-editing protein (Cas9) can be turned on only in specific cells or at specific times using a special genetic switch. Granted to Massachusetts Institute of Technology in 2025 with 16 claims, and it is expected to expire in 2041.
Coverage
What does this patent actually cover?
The patent details a "non-human transgenic animal" (ClaimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1), meaning an animal whose genes have been changed. This animal has a special genetic package, called an "exogenous conditional expression cassette," inserted into its own DNA, specifically "knocked into an endogenous genomic locus" (Claim 1), like the "Rosa26 locus" (Claim 3) in mice. This cassette contains the instructions for making a "Cas9 protein," which is a molecular scissor used in CRISPR gene editing. The clever part is that the Cas9 protein is only made when another enzyme, "Cre recombinase," is present (Claim 1). This allows scientists to control exactly when and where the Cas9 protein is active. The Cas9 protein itself is designed with two "nuclear localization signals" (NLS), one at each end (N-terminus and C-terminus), to help it get into the cell's nucleus where the DNA is (Claim 1). For example, a researcher could use this to study how turning on Cas9 in only certain brain cells affects a neurological disease.
The gap
What does this patent NOT cover?
- Does not cover genetically modifying human beings.
- Does not cover Cas9 protein expression that is always on or not dependent on Cre recombinase.
- Does not cover Cas9 proteins that lack two nuclear localization signals (NLS), one at the N-terminus and one at the C-terminus.
- Does not cover gene editing systems that use different proteins instead of Cas9 (e.g., other CRISPR enzymes or TALENs).
- Does not cover inserting the Cas9 cassette into just any random spot in the genome; it must be "knocked into an endogenous genomic locus."
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
Key facts
What made this novel
The noveltynoveltyThe requirement that an invention be different from anything publicly known before its priority date.Read more → lies in combining the precise, conditional activation of Cas9 using Cre recombinase with the specific design of the Cas9 protein itself (two NLS signals) within a "knocked-in" cassette in a living animal, enabling fine-tuned gene editing studies.
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
Transgenic mouse models for neurological disorders
Mouse models for cancer research
Rat models for cardiovascular studies
Rabbit models for eye disease research
Why it matters
The bigger picture
This technology allows scientists to create highly specific animal models for studying diseases. By controlling exactly when and where the Cas9 gene editor is active, researchers can precisely investigate the role of specific genes in particular cell types or developmental stages. This precision helps in understanding complex biological processes and testing potential gene therapies in a controlled living system, which is crucial for drug discovery and development.
Filed
April 30, 2021
Granted
March 18, 2025
Market context
Who's building on this
Companies in this space
The Massachusetts Institute of Technology (MIT), as the assigneeassigneeThe entity that owns the patent — usually the inventor's employer or a company.Read more →, continues to be a leader in CRISPR technology and its applications. Academic research institutions globally, along with biotech companies like Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics, are actively developing and utilizing advanced gene-editing tools and animal models for therapeutic discovery and validation.
Market impact
This type of technology has significantly advanced the field of genetic research by providing more precise and controllable animal models. It has enabled a deeper understanding of disease mechanisms and accelerated the preclinical development of gene therapies. The ability to activate gene editing conditionally in specific tissues has become a standard approach in many research labs, influencing drug target identification and validation across the pharmaceutical industry.
Claim 1 — Plain English
What this patent covers
The patent details a "non-human transgenic animal" (Claim 1), meaning an animal whose genes have been changed. This animal has a special genetic package, called an "exogenous conditional expression cassette," inserted into its own DNA, specifically "knocked into an endogenous genomic locus" (Claim 1), like the "Rosa26 locus" (Claim 3) in mice. This cassette contains the instructions for making a "Cas9 protein," which is a molecular scissor used in CRISPR gene editing. The clever part is that the Cas9 protein is only made when another enzyme, "Cre recombinase," is present (Claim 1). This allows scientists to control exactly when and where the Cas9 protein is active. The Cas9 protein itself is designed with two "nuclear localization signals" (NLS), one at each end (N-terminus and C-terminus), to help it get into the cell's nucleus where the DNA is (Claim 1). For example, a researcher could use this to study how turning on Cas9 in only certain brain cells affects a neurological disease.
The clever bit
The novelty lies in combining the precise, conditional activation of Cas9 using Cre recombinase with the specific design of the Cas9 protein itself (two NLS signals) within a "knocked-in" cassette in a living animal, enabling fine-tuned gene editing studies.
What it does not cover
- Does not cover genetically modifying human beings.
- Does not cover Cas9 protein expression that is always on or not dependent on Cre recombinase.
- Does not cover Cas9 proteins that lack two nuclear localization signals (NLS), one at the N-terminus and one at the C-terminus.
- Does not cover gene editing systems that use different proteins instead of Cas9 (e.g., other CRISPR enzymes or TALENs).
- Does not cover inserting the Cas9 cassette into just any random spot in the genome; it must be "knocked into an endogenous genomic locus."
Patent timeline
Application submitted to the patent office
Application published, typically 18 months after filing
Patent officially issued
Patent enters public domain
PatentBrief Score
Impact Score
Moderate
Citation count
0/40
No citations yet
Claim breadth
11/20
Broad claimsclaimsThe numbered statements at the end of a patent that legally define what the inventor owns.Read more →
Recency
20/20
Granted within 5 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
$88K – $281K
Midpoint $176K · 14.8 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
16 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Zhou, Y., Platt, R. J., Feng, G., & Zhang, F. (2025). How to Make Animals That Can Turn On CRISPR Gene Editing (U.S. Patent No. 12,252,707). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/12252707/delivery-engineering-and-optimization-of-systems-methods-and-compositions-for-se
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 to Make Animals That Can Turn On CRISPR Gene Editing cover?
This patent describes creating genetically modified non-human animals, like mice, where a key CRISPR gene-editing protein (Cas9) can be turned on only in specific cells or at specific times using a special genetic switch.
Who owns patent US 12252707?
Massachusetts Institute of Technology owns this patent, granted in 2025.
When does this patent expire?
This patent is expected to expire on April 30, 2041, when the invention enters the public domain.
What problem does this patent solve?
This technology allows scientists to create highly specific animal models for studying diseases. By controlling exactly when and where the Cas9 gene editor is active, researchers can precisely investigate the role of specific genes in particular cell types or developmental stages. This precision helps in understanding complex biological processes and testing potential gene therapies in a controlled living system, which is crucial for drug discovery and development.
What does this patent NOT cover?
Does not cover genetically modifying human beings.
Same assignee
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