Scientists have repurposed a bacterial immune response against viruses, called CRISPR, to edit the human genome in ways never before possible. Remarkably, a CRISPR gene-editing cure for sickle cell anemia has been approved by the FDA only ten years after the advent of the technology.

Understanding the Wider Scope

• In the 1980s, scientists observed repeating, palindromic sequences with unique spacers between the repeating sequences.
• The researchers called these repeats “Clustered Regularly Interspaced Short Palindromic Repeats,” or CRISPR.
• In the mid-2000s, scientists realized the spacers between CRISPR sequences matched partial DNA sequences of viruses that infect bacteria.
• CRISPR functions as a “genetic memory” of viral DNA that bacteria use to fight off viruses if reinfected.
• Researchers adapted the CRISPR-Cas system to cut DNA at a specific location in the genome.
• The technique depends on attaching Cas and a “guide RNA” to the matching genome sequence to activate Cas and cut DNA at that specific site.

Why it Matters

The exa-cel treatment developed by Vertex Pharmaceuticals and CRISPR Therapeutics uses the patient’s own bone marrow stem cells to cure sickle cell disease.The patient’s stem cells are corrected using a CRISPR technique and reintroduced to the patient to permanently create red blood cells without the sickle defect.

Exa-cel, under the brand name Casgevy, recently received FDA approval for sickle cell anemia and represents the first CRISPR treatment to be approved by the regulatory agency for use in human patients.

Tricky Terminology

The original Cas protein, Cas9, was isolated from Streptococcus bacteria, hence the name CRISPR-Cas9.

CRISPR in Action

The CRISPR system has been used to genetically modify mosquitoes to reduce malaria transmiccion and alter crops to increase resilience.

CRISPR Possibilities

• RCas9, an engineered Cas9, targets and cuts messenger RNA (mRNA), a temporary copy of DNA instructions that is used to make proteins. 
• Scientists may be able to cut disease-specific mRNAs with RCas9 and reduce the production of disease-causing proteins without altering a patient’s genome.

Cocktail Fodder

CRISPR was used by the startup eGenesis to successfully disable viruses embedded in pig DNA that could infect human transplant recipients, making potential pig donor organs safer for humans.

Other Gene Therapy Technologies

Before the approval of CRISPR technology, the FDA approved several other gene therapy tehcnologies; Luxturna and Zolgensma use AAV technology and Kymriah and Yescarta used CAR-T technology. Learn the science of AAV and CAR-T and how these technologies are applied to cure diseases such as SMA, lymphoma and retinal dystrophy in Biotech Primer’s Gene Therapy Primer.