Skip to Content
Biotechnology

The secret to a new drug could be hiding in your genes

Companies are searching gene databases for people whose DNA says they should be very sick, but who aren’t.
February 28, 2019
Dr Graham Beards | Wikipedia

 

Sickle-cell disease is caused by a one-letter spelling mistake in the hemoglobin gene. But not everyone who inherits the error suffers the worst effects of the blood disease.

By 2008, scientists had figured out why. It’s because some of them have a second genetic peculiarity that causes their bodies to continue to manufacture fetal hemoglobin, a version of the oxygen-carrying substance that’s normally made only until birth.

The second genetic change acts as a modifier—in effect, a genetic countermeasure against disease.

Now, a startup called Maze Therapeutics has amassed an impressive bank account ($191 million from investors Third Rock Ventures, ARCH Venture Partners, and others) to carry out a search for such modifiers and create drugs that mimic their effects.

The startup—which says it wants to find out why some people get sick and others don’t—plans to mine public genetic databases to locate people with gene errors who’ve not had serious medical problems.

The hunt for such genetic exceptions is one of the latest fads in drug development. It got attention in 2016 after the so-called “Resilience Project” said it had found 13 people who should have had serious childhood diseases, but didn’t. Other companies, including Regeneron Pharmaceuticals, have also staked their futures on assembling private troves of DNA data and looking for outliers.

Notably, Maze says it won’t need to create its own genetic database, a costly undertaking. Instead, it will use free public resources, including a British biobank of 500,000 people’s genes and medical records. Soon, similar data could become available from the US Department of Veterans Affairs. The company’s founders include Mark Daly, who oversees a genetics institute in Finland, a country building its own biobank.

“There is a remarkable amount of genetic data out there,” says Charles Homcy, who is CEO of Maze. “Five years ago it would have been a mistake to try this.” 

New tools also exist to search for modifiers in the lab. One of the company’s other scientific founders, Jonathan Weissman, a researcher at the University of California, San Francisco, says it’s possible to take thousands of human cells afflicted with a mutation (such as the one causing sickle-cell) and, using the gene-editing tool CRISPR, introduce a different genetic modification into each.

Then, employing novel techniques for measuring single cells, researchers can see whether any of the modifications counteracted the disease. “You take a cell with a disease-causing gene and then see if you can turn it back to normal,” says Weissman. “We can do 100,000 experiments at once because each cell is its own experiment.”

There are already examples of drugs based on the discovery of modifier genes. One treatment, called Spinraza, has been successfully treating spinal muscular atrophy, an often fatal childhood disease.

Deep Dive

Biotechnology

Muhammad bin Salman funds anti-aging research
Muhammad bin Salman funds anti-aging research

Saudi Arabia plans to spend $1 billion a year discovering treatments to slow aging

The oil kingdom fears that its population is aging at an accelerated rate and hopes to test drugs to reverse the problem. First up might be the diabetes drug metformin.

individual aging affects covid outcomes concept
individual aging affects covid outcomes concept

Anti-aging drugs are being tested as a way to treat covid

Drugs that rejuvenate our immune systems and make us biologically younger could help protect us from the disease’s worst effects.

Workers disinfect the street outside Shijiazhuang Railway Station
Workers disinfect the street outside Shijiazhuang Railway Station

Why China is still obsessed with disinfecting everything

Most public health bodies dealing with covid have long since moved on from the idea of surface transmission. China’s didn’t—and that helps it control the narrative about the disease’s origins and danger.

person carrying styrofoam box used for transporting human organs
person carrying styrofoam box used for transporting human organs

A new storage technique could vastly expand the number of livers available for transplant

It allows donor livers to be held for days—significantly longer than the standard now–and even treated if they are damaged.

Stay connected

Illustration by Rose WongIllustration by Rose Wong

Get the latest updates from
MIT Technology Review

Discover special offers, top stories, upcoming events, and more.

Thank you for submitting your email!

Explore more newsletters

It looks like something went wrong.

We’re having trouble saving your preferences. Try refreshing this page and updating them one more time. If you continue to get this message, reach out to us at customer-service@technologyreview.com with a list of newsletters you’d like to receive.