CRISPR

Francisco Mojica characterized the CRISPR locus in 1993, recognizing common features in repeat sequences that led to the term CRISPR. He later hypothesized that CRISPR is an adaptive immune system.

In March 2006, Eugene Koonin proposed a hypothetical scheme for CRISPR cascades as a bacterial immune system based on inserts homologous to phage DNA. This laid the foundation for further research in the field.

Experiments conducted on 23rd March 2007 demonstrated for the first time the role of CRISPR together with Cas9 genes in protecting bacteria against viruses, showcasing the practical application of this technology.

In August 2008, John van der Oost and colleagues discovered that spacer sequences from phages are transcribed into small RNAs called CRISPR RNAs (crRNAs), which guide Cas proteins to target DNA.

In December 2008, Luciano Marraffini and Erik Sontheimer revealed that CRISPR targets DNA, not RNA, contrary to previous assumptions. This discovery paved the way for understanding the interference mechanism of CRISPR-Cas systems.

In December 2010, Sylvain Moineau and team demonstrated that CRISPR-Cas9 creates double-stranded breaks in target DNA precisely 3 nucleotides upstream of the PAM sequence. They confirmed that Cas9 is the sole protein required for cleavage in the Type II CRISPR system.

In March 2011, Jennifer Doudna and Emmanuelle Charpentier started collaborating to study the bacterial CRISPR system, a crucial step towards the development of the CRISPR-Cas9 gene editing technology.

On May 25, 2012, UC Berkeley was the first to file a patent application for the key components of the CRISPR-Cas9 system, marking a significant milestone in the development of gene editing technology.

Doudna, Charpentier, Martin Jinek of UC Berkeley and Krzystof Chylinski of the University of Vienna file the first patent application for CRISPR-Cas9 gene editing, covering all environments such as bacteria, plants, animals, and human cells.

On 17th August 2012, a radically new gene editing method that harnessed the CRISPR-Cas9 system was published, revolutionizing the field of genetic engineering.

Six separate research teams, including Doudna’s, publish the first use of CRISPR-Cas9 gene editing in living cells, specifically human and animal cells.

In January 2013, Feng Zhang from the Broad Institute of MIT and Harvard successfully adapted CRISPR-Cas9 for genome editing in eukaryotic cells, showcasing its potential for targeted genome cleavage and homology-directed repair.

The Broad Institute is granted the initial patent for CRISPR-Cas9, specifically for applications in plant and animal cells.

CRISPR technology has become popular in the past five years, with genome engineers working on developing a highly specific and programmable platform for various biological and translational technologies.

The U.S. Patent and Trademark Office (USPTO) initiates an interference proceeding to determine if the Broad Institute's patents, including a pending application, conflict with UC's foundational patent application for CRISPR-Cas9.

On May 10, 2017, the European Patent Office (EPO) granted the University of California (UC) team the first CRISPR-Cas9 patent in the European Union (EU), covering the use of CRISPR-Cas9 in plants, animals, and human cells.

On July 25, 2017, the University of California (UC) appealed the Patent Trial and Appeal Board (PTAB) decision regarding CRISPR to the U.S. Court of Appeals for the Federal Circuit.

The European Patent Office (EPO) granted the University of California (UC) team a patent for methods and compositions related to RNA-directed target DNA modification and modulation of transcription in various settings.

The United States Patent and Trademark Office (USPTO) granted the University of California (UC) team their first patent on CRISPR-Cas9, which allows for easier use of the gene-editing tool within plant or animal cells or externally.

The US Court of Appeals affirms the USPTO's decision that the Broad Institute's patent for using CRISPR-Cas9 in plant and animal cells is distinct from UC's patent for using CRISPR-Cas9 in any environment.

The USPTO grants UC a patent covering CRISPR-Cas9 gene editing technology using single-molecule guide RNAs and its applications in any cell.

The European Patent Office (EPO) granted a patent to the University of California (UC) team for methods and compositions related to RNA-directed target DNA modification and transcription modulation in eukaryotic cells.

The United States Patent and Trademark Office (USPTO) issued a notice of allowance for a patent application covering methods of cleaving, modifying, or targeting DNA in cells using a CRISPR protein-RNA complex. The patent is scheduled to be issued on July 2, 2019.

On May 20, 2019, the USPTO granted a patent to the UC team for CRISPR methods and systems utilizing single-molecule guide RNAs in any environment. The patent covers techniques for targeting and modifying DNA using Cas9 proteins with specific mutations.

On May 21, 2019, the USPTO issued a notice of allowance for a patent application (U.S. 16/201,836) related to CRISPR methods targeting, modifying, or cleaving DNA using single-molecule guide RNAs. This further expands the scope of CRISPR technology patents.

On May 22, 2019, the USPTO issued a notice of allowance for a patent application (U.S. 16/201,855) that covers methods of producing a genetically modified cell using the Cas9 protein or DNA-targeting RNA.

On May 28, 2019, UC was granted U.S. Patent 10,301,651 for CRISPR methods that allow sequence-specific repression or activation of gene expression in various cell types.

On June 4, 2019, UC was granted U.S. Patent 10,308,961 for CRISPR methods enabling sequence-specific repression or activation of gene expression in all cell types.

The USPTO granted a patent to a UC team for CRISPR methods involving targeting and binding a target DNA, modifying a target DNA, or modulating transcription from a target DNA in a cell. The patent covers both single guide RNAs and dual guide RNAs.

On June 25, 2019, the Patent Trial and Appeal Board (PTAB) declared an interference between 10 University of California (UC) CRISPR patents and 13 Broad Institute patents, along with one Broad patent application.

July 2, 2019, saw the United States Patent and Trademark Office (USPTO) granting a patent to the UC team. The patent covers methods of cleaving, modifying, or targeting and binding DNA in a cell using a CRISPR protein-RNA complex.

On July 16, 2019, the USPTO granted the 9th patent to the UC team. This patent covers methods of producing a genetically modified cell by introducing the Cas9 protein or a nucleic acid encoding it, along with a single molecule DNA-targeting RNA.

On July 23, 2019, the USPTO granted two patents to the UC team. The first patent involves targeting and modifying a target DNA using single-molecule guide RNAs, while the second patent covers CRISPR methods for modifying DNA with a Cas9 protein containing mutations in key domains.

On September 3, 2019, the US Patent and Trademark Office (USPTO) granted a patent to the UC team, increasing their total portfolio to 11. The patent covers nucleic acid molecules encoding single-molecule guide RNAs and CRISPR-Cas9 compositions.

On September 10, 2019, the US Patent and Trademark Office (USPTO) granted another patent to the UC team, bringing their total portfolio to 12. This patent covers compositions of single-molecule, DNA-targeting RNA (sgRNA) and Cas9 protein or nucleic acid encoding the Cas9 protein.

The University of California (UC) received the U.S. Patent 10,421,980, expanding their patent portfolio to 15. This patent likely involves DNA-targeting RNAs with defined lengths that hybridize with Cas9 proteins to target specific DNA sequences and methods for modifying or modulating transcription from target DNA.

On October 15, 2019, the US Patent and Trademark Office granted a patent to the UC team, increasing their total CRISPR-Cas9 patent portfolio to 17. This patent specifically covers methods and compositions for RNA-directed target DNA modification and modulation of transcription.

On November 26, 2019, the US Patent and Trademark Office granted another patent to the UC team, further expanding their CRISPR-Cas9 patent portfolio. This patent covers methods of targeting, binding, and cleaving target DNA in prokaryotic cells using Cas9 protein and single molecule DNA targeting RNAs.

On December 24, 2019, the USPTO granted a patent to the UC team, increasing their total portfolio to 19. The patent covers compositions and kits with Cas9 and DNA-targeting RNA.

On December 31, 2019, the USPTO granted a patent to the UC team, bringing their total portfolio to 20. The patent covers methods of producing a genetically modified cell.

In 2020, The Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for their development of CRISPR-Cas9 as a powerful gene-editing tool.