Gene Editing to Treat Disease

The majority of medical therapies available today are directed at managing disease processes, the pathogenic or mis-regulated proteins or molecules associated with disease. However, these pathogenic molecules themselves are typically encoded in or affected by changes in genes or other sequences in the human genome, which encompasses the DNA in all our cells. Gene editing technologies, including CRISPR/Cas9, now offer us the ability to directly modify or correct the underlying disease-associated changes in our genome. Successfully editing or correcting a gene that encodes the dysfunctional or missing protein can in principle result in the expression of a fully normal protein and full correction of the disease.

Gene therapy and other technologies to modify the genome have been in development for many years, and a small number of gene therapies have been approved to treat patients. However, these older approaches have been burdened by challenges to their safety and efficacy and have not yet provided the ability to precisely control a range of different genetic changes.

We believe that CRISPR/Cas9 offers just such an opportunity, particularly to correct DNA changes in somatic (non germ line) cells in patients with serious disease.

CRISPR/Cas9 is a rapid and easy to use gene editing technology that can selectively delete, modify or correct a disease causing abnormality in a specific DNA segment. CRISPR refers to Clustered Regularly Interspaced Short Palindromic Repeats occurring in the genome of certain bacteria, from which the system was discovered; Cas9 is a CRISPR-associated endonuclease (an enzyme), the molecular scissors that are easily programmed to cut and edit, or correct, disease-associated DNA in a patients cell. The location at which the Cas9 molecular scissors cut the DNA to be edited is specified by guide RNA, which is comprised of a crRNA component and a tracrRNA component, either individually or combined together as a single guide RNA (sgRNA). For example, a guide RNA can direct the molecular scissors to cut the DNA at the exact site of the mutation present in the genome of patients with a particular genetic disease. Once the molecular scissors make a cut in the DNA, additional cellular mechanisms and exogenously added DNA will use the cells own machinery and other elements to specifically repair the cut DNA.

There are more than 10,000 known single-gene (or monogenic) diseases, occurring in about 1 out of every 100 births1. Scientists and clinicians are now conducting pioneering research using CRISPR/Cas9 to address both recessive and dominant genetic defects, opening up the potential of gene editing to provide novel transformative gene-based medicines for patients with a large number of both rare and common diseases.

Dr. Emmanuelle Charpentier, one of CRISPR Therapeutics scientific founders, co-invented the CRISPR/Cas9 technology.

The clustered repeats of CRISPR were discovered in 1987 in bacteria2, but their function was unknown. In 2000, these clustered repeat elements were found to be relatively common in bacteria3 hinting to an important role of these elements. The clustered repeats were given the name CRISPR in 2002 and multiple CRISPR-associated (Cas) genes were discovered adjacent to the repeat elements in that same year4.

CRISPR/Cas9 is a rapid and easy to use gene editing technology that can selectively delete, modify or correct a disease causing abnormality in a specific DNA segment. CRISPR refers to Clustered Regularly Interspaced Short Palindromic Repeats occurring in the genome of certain bacteria, from which the system was discovered; Cas9 is a CRISPR-associated endonuclease (an enzyme), the molecular scissors that are easily programmed to cut and edit, or correct, disease-associated DNA in a patients cell. The location at which the Cas9 molecular scissors cut the DNA to be edited is specified by guide RNA, which is comprised of a crRNA component and a tracrRNA component, either individually or combined together as a single guide RNA (sgRNA). For example, a guide RNA can direct the molecular scissors to cut the DNA at the exact site of the mutation present in the genome of patients with a particular genetic disease. Once the molecular scissors make a cut in the DNA, additional cellular mechanisms and exogenously added DNA will use the cells own machinery and other elements to specifically repair the cut DNA.

There are more than 10,000 known single-gene (or monogenic) diseases, occurring in about 1 out of every 100 births1. Scientists and clinicians are now conducting pioneering research using CRISPR/Cas9 to address both recessive and dominant genetic defects, opening up the potential of gene editing to provide novel transformative gene-based medicines for patients with a large number of both rare and common diseases.

Dr. Emmanuelle Charpentier, one of CRISPR Therapeutics scientific founders, co-invented the CRISPR/Cas9 technology.

The clustered repeats of CRISPR were discovered in 1987 in bacteria2, but their function was unknown. In 2000, these clustered repeat elements were found to be relatively common in bacteria3 hinting to an important role of these elements. The clustered repeats were given the name CRISPR in 2002 and multiple CRISPR-associated (Cas) genes were discovered adjacent to the repeat elements in that same year4.

The function of the CRISPR-Cas system in bacteria as an immune defense mechanism was hypothesized by Mojica in 20055 and experimentally validated at the food ingredient company, Danisco, in 20076.

In 2011, Dr. Charpentiers lab discovered an essential component of the CRISPR-Cas system, tracrRNA, in bacteria7. The following year she and colleagues described how the Cas9 endonuclease works together with crRNA and tracrRNA to form functional molecular scissors to cut at a specific DNA sequence in the genome8. In this same publication the authors also described how to modify, or re-program, the system to direct the molecular scissors to cut at essentially any DNA sequence; how to modify the RNA components into a single guide RNA, simplifying the system into only 2 components; and how to modify the Cas9 molecular scissors to make nicks in the DNA by only cutting one of the two DNA strands. These foundational discoveries enabled transformative gene editing in a wide range of cells, tissues and species, including for the potential benefit of patients suffering from serious genetic diseases.

CRISPR/Cas9 is an easy, effective technology for gene editing that has enabled a wide range of new studies and transformed many areas of research. Thousands of academic laboratories across the world are carrying out research using the technology. Rapid adoption of CRISPR/Cas9 by the broader academic community and the collective efforts of their research are in turn driving tremendous progress in the field.

We have licensed the foundational CRISPR/Cas9 patent estate for human therapeutic use from our scientific founder, Dr. Emmanuelle Charpentier. This IP is directed broadly to CRISPR/Cas9 genome editing and includes many different applications of the technology. We have filed additional IP and will continue to do so in support of our mission to bring transformative gene-based medicines to patients with serious diseases.

In 2011, Dr. Charpentiers lab discovered an essential component of the CRISPR-Cas system, tracrRNA, in bacteria7. The following year she and colleagues described how the Cas9 endonuclease works together with crRNA and tracrRNA to form functional molecular scissors to cut at a specific DNA sequence in the genome8. In this same publication the authors also described how to modify, or re-program, the system to direct the molecular scissors to cut at essentially any DNA sequence; how to modify the RNA components into a single guide RNA, simplifying the system into only 2 components; and how to modify the Cas9 molecular scissors to make nicks in the DNA by only cutting one of the two DNA strands. These foundational discoveries enabled transformative gene editing in a wide range of cells, tissues and species, including for the potential benefit of patients suffering from serious genetic diseases.

CRISPR/Cas9 is an easy, effective technology for gene editing that has enabled a wide range of new studies and transformed many areas of research. Thousands of academic laboratories across the world are carrying out research using the technology. Rapid adoption of CRISPR/Cas9 by the broader academic community and the collective efforts of their research are in turn driving tremendous progress in the field.

We have licensed the foundational CRISPR/Cas9 patent estate for human therapeutic use from our scientific founder, Dr. Emmanuelle Charpentier. This IP is directed broadly to CRISPR/Cas9 genome editing and includes many different applications of the technology. We have filed additional IP and will continue to do so in support of our mission to bring transformative gene-based medicines to patients with serious diseases.

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