Last week, the FDA approved the use of gene-editing treatment for the first time. The two gene therapies that were approved are used to treat a severe form of sickle cell disease, a “rare, debilitating and life-threatening blood disorder.”

The gene therapies are made possible by a new technology called CRISPR, which has been described as a “cut & paste tool for DNA editing.”

Victoria Gray, a woman with sickle cell disease who became the first American to receive the gene therapy, said:

So, what is this remarkable technology that’s changing lives — and maybe even the way that we pass genes onto the next generation?

What is CRISPR?

The term ‘CRISPR’ is now used to refer to gene-editing technologies, but the full name comes from natural biological phenomena discovered by researchers over the past few decades.

CRISPRs, which stand for “Clustered Regularly Interspaced Short Palindromic Repeats,” are essentially a part of bacterial immune systems that defend against invading viruses. They are made of repeating genetic code sequences that are interrupted by so-called “spacer” sequences, which contain genetic code from previous viruses — or from genetic modification by humans.

If CRISPR isn’t already a mouthful, the full name is CRISPR-Cas9. Cas9 refers to a specific enzyme that acts as a pair of molecular scissors to cut DNA strands in the genome so that small pieces of DNA can be added or removed.

Thanks to CRISPR-Cas9 techniques, scientists can insert what is called a “gene drive” — a specific genetic insertion that is inheritable to future generations. In the case of the FDA-approved sickle cell therapy, the genes of patients are changed in order to restore normal red blood cell production in their bodies and alleviate sickle cell symptoms.

The history of CRISPR and gene-editing

Naturally-occurring CRISPRs were first discovered in e. coli bacteria in 1987, but little was known about these DNA fragments or how they worked. As researchers learned more about CRISPRs, some began to speculate about whether they could be used as a genomic editing tool.

The possibility of using the Cas9 protein as “genetic scissors” was identified in 2005, around the same time that some scientists began to experiment with using CRISPRs to edit the genome of yoghurt bacteria.

Research into so-called crRNA (or CRISPR-associated RNA) identified the molecules that guide the Cas proteins to the specific DNA sequences matching the viral genetic material.

Finally, the discovery of a short RNA molecule called tracrRNA in 2011 allowed for the creation of functional CRISPR-Cas9 systems in labs.

In 2020, CRISPR researchers Jennifer Doudna and Emmanuelle Charpentier won the Nobel Prize in Chemistry for their work on developing CRISPR-Cas9 systems for gene editing.

The Nobel committee said that their research in developing CRISPR has enabled:

How is CRISPR being used to prevent disease?

One of the first uses that researchers developed for CRISPR was in preventing the spread of malaria, dengue, and other diseases by mosquitoes.

While most people in the developed world see mosquitoes as a mere annoyance, they pose a deadly threat to millions of people — especially children — across South America, Africa, and Asia.

In 2015, researchers at the University of Missouri created a genetic mutation in mosquitoes that would prevent them from carrying and transmitting viruses like dengue.

Earlier this year, experiments with releasing gene-edited mosquitoes into the wild in Colombia were found to reduce dengue infection rates by up to 97% in some Colombian cities.

CRISPR babies and genetically modifying humans

Some researchers are exploring whether CRISPR can be used to treat or prevent Alzheimer's disease. Even if this and similar research is successful, there are several factors slowing the adoption of gene therapy for humans.

Gene-editing procedures for humans are difficult, painful, and costly. Patients must undergo multiple tests before receiving a potentially risky bone marrow transplant.

There are also concerns about the unintended consequences of genetically modifying humans. CRISPR could introduce unwanted mutations or outright damage the human genome, potentially harming people in unforeseeable ways.

In 2018, Chinese researchers claimed to have produced genetically modified CRISPR babies that were given genetic resistance to HIV. That news, along with speculation about wealthy families using CRISPR to genetically modify their children (a practice known as germ-line editing), has raised concerns about the dystopian possibilities that gene-editing enables.

A World Health Organization committee that was established after news of the CRISPR babies was publicized has issued guidelines for gene-editing research that bar researchers from using gene therapy on human embryos for safety reasons.

Jennifer Doudna, one of the 2020 Nobel Prize winners, condemned the Chinese lab’s decision to use CRISPR to alter the human genome and reiterated earlier calls for a moratorium on germ-line editing in humans. She said that the Chinese research revealed that, “human embryo editing is relatively easy to achieve, [but that] it is difficult to do well and with responsibility for lifelong health outcomes.”

LEARN MORE: Doudna's 2017 book A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution would be a great place to start. Or, check out one of her TED Talks here:

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Dan