Since the human genome was first mapped, scientists have identified the individual genes responsible for approximately 7,000 genetic disorders, many of which can drastically impair an individual’s quality of life or reduce life expectancy. The Centers for Disease Control and Prevention reports that genetics play a role in nine of the ten leading causes of death in the United States, most notably chronic conditions such as cancer, diabetes and heart disease.
The development in 2012 of CRISPR/Cas9 as a genome editing tool by one of Intellia’s founders, Jennifer Doudna, has triggered unprecedented scientific research on how to apply this technology to revolutionize medical care and treatment. This work is rapidly leading to the development of a new class of therapeutic options for patients with chronic diseases.
The ideal genome editing technology
CRISPR/Cas9 technology makes possible the precise and targeted modification of the genetic material of cells. Genome editing works by using an enzyme to make a cut at a chosen site in the genome, followed by the deletion, repair or insertion of genetic material at that site, to restore cellular function facilitated by the cell’s natural DNA repair mechanisms.
“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; Founder, Intellia Therapeutics
CRISPR/Cas9 genome editing has the potential to treat a broad range of diseases that are not adequately addressed by current therapies.
Given its permanent effects on DNA, genome editing could potentially cure a disease with a single treatment. This represents a significant advantage over today’s medicines targeting genetic diseases, which commonly offer only temporary relief, must be repeated often, or are taken for an entire lifetime.
Additionally, unlike gene therapy, which typically involves introducing additional DNA into a patient’s cells to address the genetic deficiency, genome editing can make permanent, precise changes in the patients’ chromosomes, stably repairing the underlying genetic mutation. Furthermore, genome editing can remove or repair anomalous genes that drive diseases, which gene therapy typically cannot. These attributes of genome editing may provide a significant competitive edge over gene therapy, more closely mimicking the body’s own repair system while also addressing a broader spectrum of diseases.
Attributes and therapeutic potential
Unlike more cumbersome and costly earlier-generation genome editing technologies, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the CRISPR/Cas9 system is simple. CRISPR/Cas9’s potential stems not only from this simplicity, but also from its selectivity, broad applicability, rapid optimizability, scalability and multifunctional programmability.
|KEY ENABLING ATTRIBUTES TO BECOME
NEXT BIG DRUG CLASS
|BROADEST POTENTIAL TO MODULATE GENES|
|High potency (cleavage efficiency) and specificity||Ability to target multiple DNA sites simultaneously|
|Broad applicability to both in vivo and ex vivo applications||Multiplexing potential to address complex genetic disorders|
|Simple editing tools (guide RNA plus protein) allow unprecedented ability to scale and optimize||Multifunctional programmability: knockout, insert or repair genes|
|Potential one-time curative treatment|
How it works
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 cleave the targeted DNA sequence
- The guide RNA, which recognizes the specific target DNA sequence, allowing the Cas9 scissors to cut.
Upon cleavage, the natural cellular repair processes come into play to result in knockout, repair, or insertion of genetic material.