The age of genetic medicine
The big idea
The technology behind Covid-19 vaccines could spur advances in treating cancer, HIV, and rare diseases.
By the digits
2: Vaccines using mRNA that have emergency use authorization in the US
9: precision genetic therapies approved for use in the US
4: CAR-T therapies currently on the market, all to treat blood cancers
~4,000: Types of receptors our cells have, to which genetic drugmakers have to match proteins on the outside of their drugs
100s: Number of small biotech companies focused on delivering genetic medicine that have popped up globally since 2010
10: Vaccines for infectious diseases biotech company Moderna currently has in the works
$2.1 million: Lifetime cost of Zolgensma, a genetic therapy approved by the FDA, for a single patient
Commonly held question
How does genetic medicine work?
Both the Pfizer and Moderna Covid-19 vaccines use messenger RNA (mRNA) to instruct our cells to make a new protein—in this case, the spike protein on the SARS-CoV-2 virus—so our immune systems respond to it like a threat.
But there are other ways to use or alter genetic material to improve a patient’s health. Scientists can:
- Extract certain cells, modify them with gene editing enzymes like Crispr, and then reintroduce them to our bodies
- Insert a new gene to make up for a faulty one using a benign, modified virus to sneak into our cells (these are called gene therapies, and they were some of the earliest iterations of genetic medicine)
Each of these methods presents its own challenges. Here are a few:
- Crispr could cause an immune reaction, which could potentially cause more damage
- Some scientists and patients balk at the idea of permanently changing our genetic master code in select cells. Even if it works, it’s a cumbersome process, and if a mistake happens, it’d be permanent for the cell’s lifetime (although notable, these therapies could never jump to non-targeted cells)
- There are problems with delivery. Getting the treatment to the right cells is difficult. We need a much larger amount of genetic material to tell our cells to make a certain protein than existing small molecule drugs. The mRNA has to be encapsulated in something (usually lipid nanoparticles) so it’s not attacked by the body, are hard to engineer.
One big number
25 times: Size of genetic material needed to tell our cells to make a certain protein compared to small molecule drugs. It’s one of the reasons genetic medicine is so difficult to engineer.
What diseases could genetic medicine treat?
There are three fields for which genetic medicine offers particularly promising innovations:
- Immunizations. Yes, mRNA vaccines are useful to fight Covid-19, but in the future they could make up antidotes for snake venom and treat infectious diseases like HIV, tuberculosis, and the flu. Such vaccines could save millions of lives per year.
- Cancer therapies. Cancer normally evades the immune system, but introduced mRNA could help the body recognize the cancer so it can then attack it. This would be a dramatic upgrade from current chemotherapies because, instead of flooding the body with toxic chemicals that kill both cancerous and healthy cells, cancer vaccines could target only the cancer itself, leaving the rest of the body alone.
- Rare genetic diseases. When a disease starts in the genome—or in the process of turning the genome into healthy cells—it makes sense to treat it at its source. Once doctors figure out the problem, they can develop and introduce therapies that will fix the way human cells interpret broken code.
Person of interest: Mila Makovec
In 2016, Mila Makovec was a sunny six-year-old with a rare condition called Batten disease. Though Mila had developed normally as a toddler, her disease caused her to slide backward; her speech, gait, and vision had become increasingly impaired. After three years of symptoms, no doctor had been able to treat her.
After analyzing Mila’s genome, physician-scientist Timothy Yu and his collaborators found the cause of her disease: a bit of extra DNA in one of the genes Mila needed to rid herself of cellular waste, which led to a mistake in the mRNA reading it, and ultimately the protein it formed. Knowing that was the culprit, Yu’s team developed a treatment that could fix the reading error. It wasn’t a permanent fix—her DNA would always carry the mutation—but the treatment worked to quiet its mistakes in her brain cells’ nuclei. The process of identifying the target and creating a bespoke therapy took just over eight short months.
Through infusions in her spinal fluid every two to four months, Yu and his colleagues were able to mitigate some of Mila’s symptoms. Unfortunately, much of the disease’s damage had already been done, and Mila passed away earlier this year. Mila’s case, while tragic, is an important datapoint: A fatal genetic condition like hers could be successfully treated in a matter of months. In this case, the ultimate shortcoming of the genetic therapy was connecting Mila and her family to the right doctors in time.
Brief history of genetic medicine
1953: UK-based biologists John Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin uncovered the double helix structure of DNA.
1965: Robert William Holley, Har Gobind Khorana, and Marshall Warren Nirenberg become the first to sequence genetic material—a form of RNA. They win the Nobel Prize for their work in 1968.
1971: Cetus, the first biotech company, is established in Berkeley, California, working on components of antibiotics. It’s the first of the third wave of pharmaceuticals: biologics, drugs are based on molecules the body makes, like insulin or antibodies. They set the groundwork for the fourth wave of pharmaceuticals—precision genetic medicine—which kicked off in the 2000s.
1998: The first form of precision genetic medicine, an ASO called fomivirsen to treat a rare form of eye inflammation in people with compromised immune systems, is cleared for medical use in the US.
2016: The FDA approves Spinraza, an antisense oligonucleotide drug to treat the fatal genetic disease spinal muscular atrophy. It is the second precision genetic treatment to receive such an approval.
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