History
The development in 2012 of CRISPR/Cas9Adapted from a naturally occurring bacterial immune system, CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. One of the proteins in the CRISPR system is known as CRISPR-associated 9 protein or Cas9 protein, which acts as a pair of ‘molecular scissors’ to cleave DNA. Researchers have co-opted the bacterial CRISPR/Cas9 system to make specific changes in the DNA of humans, other animals and plants. CRISPR/Cas9 was first harnessed in 2012 as a genome editing tool in the lab. More recently, scientists have begun engineering and testing CRISPR systems to be very specific to a desired genetic target. as a genome editingAlso called gene editing. Genome editing collectively refers to a set of technologies, including CRISPR/Cas9, that can be used to cut and modify DNA. Genome editing uses systems to make the DNA change inside the cell. These cells can be edited in the body (in vivo) or outside the body (ex vivo) from a patient or donor. tool by a research team co-led by one of Intellia’s founders, Jennifer Doudna, triggered unprecedented scientific research on the application of this technology to revolutionize medical care and treatment. This technology is rapidly leading to the development of a new class of therapies for patients with genetic and oncological diseases.
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“We may be nearing the beginning of the end of genetic diseases.”
Jennifer Doudna, Ph.D., Professor of Chemistry and Molecular and Cell Biology, University of California; Chemistry Nobel Laureate, 2020; Co-founder, Intellia Therapeutics |
CRISPR/Cas9: The Ideal Genome Editing Technology
GenomeA genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than three billion DNA base pairs—is contained in all cells that have a nucleus. editing is efficient, precise and scalable.
CRISPR/Cas9 genome editing can make permanent, precisely targeted changes in patients’ chromosomes and repairCorrection of “misspelled” disease-driving DNA sequence using a CRISPR/Cas9-based gene editing therapy. the underlying genetic mutation, whereas more traditional gene therapyType of therapy where healthy genetic code is incorporated into the patient’s body with the goal of treating or preventing disease, reducing further damage and pain or potentially curing the patient. If a mutated gene causes a protein to function poorly, gene therapy may be able to restore the function of the protein. Precise gene insertion has the potential to overcome limitations of traditional gene therapy that uses adeno-associated virus (AAV) or lenti/retrovirus to deliver genetic code to its target. typically involves introducing a non-permanent copy of a gene into patients’ cells. These attributes of CRISPR/Cas9 provide a significant therapeutic edge over other gene therapy and costly earlier-generation genome editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases.
Intellia’s proprietary CRISPR/Cas9 system could potentially address diseases with a single dose of treatment because it permanently repairs the defective DNAAcronym for deoxyribonucleic acid, the hereditary material in humans and almost all other organisms. DNA can be found in the cell nucleus and contains the genetic instructions for the development, functioning, growth and reproduction of all known organisms. Nearly every cell in a person’s body has the same DNA.. This represents a breakthrough improvement over current therapies, most of which require lifelong administration because they cannot correct underlying causes of the disease.
Genome Editing Drug Development: Disease & Target Selection
How Does CRISPR/Cas9 Work?
There are two main components to the CRISPR/Cas9 genome editing system:
- The Cas9 protein, which initially recognizes the DNA and also acts like a pair of “molecular scissors” that precisely cleaves the targeted DNA sequence.
- The guide RNAAlso known as gRNA. gRNA is one of two components comprising Intellia’s CRISPR/Cas9 gene editing system. Intellia researchers are applying this modular system to several experimental medicines by changing only the gRNA sequence to reprogram for a specific genetic target., which guides the Cas9 scissors to the desired target DNA sequence and activates the scissors so they cut.
CRISPR’s Origin: Found in Nature as Part of Bacteria’s Immune System
Intellia has co-opted the bacterial immune system by identifying the key components (pictured above) and applying them to human DNA. Upon DNA cleavage, the natural cellular repair processes come into play to result in knockoutInactivation/deletion of a DNA sequence using a gene editing technology, such as the CRISPR/Cas9 system. This is the type of gene edit employed by NTLA-2001., repair or insertionInsertion of a new DNA sequence into the genome to manufacture a desired protein using a gene editing technology, such as the CRISPR/Cas9 system. of genetic material. Click here to watch how CRISPR/Cas9 works.