“”This is a major milestone for patients,” says Jennifer Doudna of the University of California, Berkeley, who shared a Nobel Prize for her work helping develop CRISPR.
“While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place,” Doudna says.
CRISPR has already been shown to help patients suffering from the devastating blood disorders sickle cell disease and beta thalassemia. And doctors are trying to use it to treat cancer and to restore vision to people blinded by a rare genetic disorder.
But those experiments involve taking cells out of the body, editing them in the lab, and infusing them back in or injecting CRISPR directly into cells that need fixing.
The study Doherty volunteered for is the first in which doctors are simply infusing the gene-editor directly into patients and letting it find its own way to the right gene in the right cells. In this case, it’s cells in the liver making the destructive protein.
“This is the first example in which CRISPR-Cas9 is injected directly into the bloodstream — in other words systemic administration — where we use it as a way to reach a tissue that’s far away from the site of injection and very specifically use it to edit disease-causing genes,” says John Leonard, the CEO of Intellia Therapeutics, which is sponsoring the study.
Doctors infused billions of microscopic structures known as nanoparticles carrying genetic instructions for the CRISPR gene-editor into four patients in London and two in New Zealand. The nanoparticles were absorbed by their livers, where they unleashed armies of CRISPR gene-editors. The CRISPR editor homed in on the target gene in the liverand sliced it, disabling production of the destructive protein.“
“Although it’s too soon to know whether the CRISPR treatment will ease the symptoms of the disease, known as transthyretin amyloidosis, the preliminary data reported today are generating excitement about what could be a one-time, lifelong treatment. “These are stunning results,” says gene editing researcher and cardiologist Kiran Musunuru of the University of Pennsylvania, who was not involved in the trial. “It exceeds all my expectations.”
The work also marks a milestone for the race to develop treatments based on messenger RNA (mRNA), the protein-building instructions naturally made by cells. Synthetic mRNAs power two COVID-19 vaccines being given to millions of people to fight the coronavirus pandemic, and many companies are working on other mRNA vaccines and drugs. The new treatment, which includes an mRNA encoding one of CRISPR’s two components, “begins the convergence of the fields of CRISPR and mRNA,” says cardiovascular researcher Kenneth Chien of the Karolinska Institute, a co-founder of Moderna, which makes one of the COVID-19 vaccines and is also developing mRNA drugs. “
Comment: Am I mistaken in thinking this is a really big deal? The usual collection of naysayers will join in the cuckoo’s song to pooh pooh the whole thing. pl