What is CRISPR?
CRISPR is a dynamic, versatile tool that allows us to target nearly any genomic location and potentially repair broken genes. But what exactly is CRISPR? How does it work?
CRISPR technology uses a protein-RNA complex composed of either the protein Cas9 or Cpf1, each of which binds to a guide RNA (gRNA) molecule that has been designed to recognize a particular DNA sequence.
How does CRISPR work?
Cas9 and Cpf1 can be reprogrammed to different sites or multiple sites using multiple gRNAs. The availability of the different engineered variants of Cas9 and Cpf1 allows for different types of cuts for genome editing, which include the following:
Cut & Revise and Cut & Remove typically result in disruption of a problematic gene or elimination of a mutation. These approaches leverage the cell’s natural DNA repair mechanisms known as non-homologous end joining, or NHEJ, to complete the edit.
When a cell repairs a DNA cut by NHEJ, it leaves small insertions and deletions at the cut site, collectively referred to as indels. NHEJ can be used to either cut and revise the targeted gene or to cut and remove a segment of DNA. In the ”cut and revise” process, a single cut is made. In the ”cut and remove” process, two cuts are made, which results in the removal of the intervening segment of DNA. This approach could be used to delete either a small or a large segment of DNA depending on the type of repair desired.
The second mechanism – our Cut & Replace approach – leverages a different DNA repair mechanism known as homology directed repair, or HDR. In this approach, a DNA template is also provided, one that is similar to the DNA that has been cut. The cell can use the template to construct reparative DNA, resulting in the replacement of a defective genetic sequence with the correct one.
What makes us different?
Advantages of our genome editing platform
In order to fully realize the broad potential of CRISPR technology to develop genomic medicines, we must be able to do the following:
edit a wide range
Reach the site
At Editas Medicine, we have developed a proprietary genome editing platform consisting of four interrelated components that are designed to meet these goals. Each component is underpinned by several specific technologies and capabilities. With our platform, we are able to design and optimize each element of our products necessary to achieve the desired edit, including the type of Cas9 or Cpf1, the sequence and structure of the guide RNA(s), the delivery vector, and elements to control expression in cells and drive the desired repair mechanism.
Cpf1 complements our expanding toolbox of CRISPR enzymes, increasing our ability to target additional disease mutations. This new enzyme uses a smaller, simpler guide-RNA, does not include a tracrRNA, and produces a different type of cut at the target DNA.
What would CRISPR medicines look like?
Medicines utilizing CRISPR technology are likely to come in a variety of configurations that open the door to treating a wide range of diseases. They can be designed and optimized to provide efficient and tightly controlled delivery to the desired tissue or cell type. Our strategy is to leverage existing delivery technologies to target the relevant cell types while also exploring a variety of next-generation delivery approaches.