Analysis | A Refreshing Gamble on Crispr Delivery

Photo of author

By Amit


For years, we’ve known that genetic diseases could one day be cured by technologies like Crispr. But there has always been a catch: These technologies can only fix the genome in the parts of the body that they can reach, and right now, their reach is very limited. Pick your favorite flavor of genetic therapy — Crispr, mRNA, siRNA, DNA — and they all have the same delivery problem. The liver, eyes and blood — those are the main places where cures might be possible.

But after about 20 years of incremental progress, there’s a chance of something entirely new. A privately held biotech company called Aera Therapeutics came out of stealth recently to debut a type of protein nanoparticle that it believes can be used to ferry all sorts of genetic medicines around the body.

Aera’s approach is very early and could ultimately fail. But its fresh take is welcome in a field that desperately needs to solve its delivery problem.

The fundamental issue with genetic medicines is that our bodies have evolved to keep bad things out of our cells. That’s great for staving off viruses or other pathogens, but also makes it incredibly hard to sneak a medicine in.

So hard, in fact, that scientists have been stuck using the same kinds of packaging for technologies like mRNA or Crispr or DNA. They largely rely on viral vectors, which are basically hollowed out shells of a virus, and lipid nanoparticles, which can be thought of as fatty bubbles that encase genetic material. But they can only efficiently deliver to certain ZIP codes — with a few exceptions, lipid nanoparticles’ routes are largely limited to the liver and the eye, for example.

In addition to where they can travel, those packages have other limitations, for example how much cargo they can hold. Some genes that scientists would like to fix are too big to fit inside a virus, and similarly, it can be tough to squeeze the instructions for making Crispr tools into a lipid nanoparticle.

Some methods avoid the delivery problem altogether by taking cells out of the body, editing them in a lab, and giving them back to patient. But that strategy is lengthy, expensive and tough on patients.

That’s why an entirely new delivery system, even one that’s still so early in development, is so welcome. Aera is capitalizing on a recent discovery about a class of human proteins that are relics of viruses that infected humans ages ago. Researchers found one of these proteins assembled into a capsid, or little protective shell, that stored the RNA needed for making more copies of itself.

Massachusetts Institute of Technology scientist Feng Zhang, one of the inventors of Crispr, saw in the discovery an opportunity to exploit the system to deliver genetic material of his choosing. His lab scoured the human genome for recipes for other proteins that assemble into protective shells and probed whether they were capable of transferring RNA. In 2021, they showed that one of those, called PEG10, could be repurposed to deliver gene-editing tools to cells.

That work became the foundation for Aera, which has raised $193 million to try to turn that academic effort into a commercial one. Chief executive Akin Akinc and board chair John Maraganore both hail from Alnylam, a company that has spent many years working on the problem of delivering another kind of genetic medicine called small interfering RNAs.

If Aera succeeds, the capsid packages could delivery gene therapies to all sorts of places. So far, around 50 of these self-assembling proteins have been found, and Akinc believes more are likely out there waiting to be discovered. The capsids these proteins form come in a range of sizes, meaning some might be better suited for slipping across the blood-brain barrier, for example, while others might be good for packing in larger pieces of genetic material.

They’re also, in theory, adaptable: Scientists have gotten very good at engineering proteins to do specific jobs, so it’s reasonable to think Aera researchers could engineer the capsids to travel to specific organs or tissues. Right now, the company is prioritizing getting to the brain, heart and muscles, all areas where genetic therapies would open a new era of medicine. And because these proteins are already floating around in our bodies, the hope is that they won’t trigger an immune reaction.

Getting there will take time. Aera has 50 researchers working on the problem, and plans to hire another 30 people this year. Even then, the technology is still several years away from being used in an actual drug.

But regardless of whether Aera succeeds at turning any of this into something commercially viable, the industry should take note. After 20 years of incremental progress, the millions of people with genetic diseases need more fresh thinking, not more of the same.

More From Lisa Jarvis at Bloomberg Opinion:

• Another Crispr First: New Treatment Wipes Out Teen’s Cancer

• Preschoolers Are Eating Their Parents’ Pot Gummies

• CDC Report on Teen Mental Health Is a Red Alert

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry. Previously, she was executive editor of Chemical & Engineering News.

More stories like this are available on

Source link

Leave a Comment