Penn CRISPR science is the foundation for a gene-editing heart disease treatment under Eli Lilly

What if a heart attack and lifetime of statin drugs could be avoided with a one-time, two-hour infusion?

Kiran Musunuru, a University of Pennsylvania cardiologist and leading gene-editing researcher, thinks it’s possible.

Musunuru cofounded Verve Therapeutics, a company developing a therapy that uses gene editing to essentially turn off one of the liver genes that produces LDL, or bad cholesterol.

Eli Lilly in June announced plans to acquire Boston-based Verve for up to $1.3 billion.

The deal is a sign that one of the largest pharmaceutical companies, known for its blockbuster diabetes and weight-loss drugs Mounjaro and Zepbound, sees promise in genetic therapies like Verve’s.

Musunuru is not employed by Verve, which he helped to found in 2018, but serves as a scientific adviser and has a financial stake in the company. At Penn, he remains deeply entrenched in advancing the science powering Verve’s therapy.

The approach uses CRISPR, a gene-editing technology that allows scientists to alter DNA. It is named after a stretch of genetic code utilized — “Clustered Regularly Interspaced Short Palindromic Repeats.”

CRISPR works like a biological find-and-replace tool, and can be programmed to find a specific irregularity within a strand of DNA, then cut it out or replace the incorrect letter.

Musunuru and colleagues at Children’s Hospital of Philadelphia recently published the outcome of a landmark case in which they developed a custom CRISPR treatment for an infant, named Baby KJ, who was born with a rare metabolic disorder that prevented him from processing protein.

» READ MORE: CHOP and Penn treated an infant with a rare disease by editing his genes

The Penn and CHOP team designed KJ’s CRISPR treatment to find and correct a genetic misspelling in a liver enzyme.

Their success captured international attention for its potential to treat rare disorders. But Musunuru says CRISPR’s potential is much broader.

Heart disease has become a leading cause of death, and Musunuru thinks it could be addressed with a two-hour CRISPR infusion.

“Why are we waiting for someone to have a heart attack?” he said. “What if you give them a one-time treatment and their cholesterol levels are permanently lower?”

The Inquirer spoke to Musunuru about what’s next for CRISPR technology.

The therapy embeds CRISPR components into lipid nanoparticles — essentially tiny soap bubbles — that are infused into the bloodstream.

The nanoparticles also contain mRNA, a type of genetic molecule that acts as a GPS to guide the CRISPR components to their target, a liver gene that produces so-called bad LCL cholesterol.

» READ MORE: Penn scientists are honored for mRNA research used in COVID vaccines

“We give it a 20-letter address, the location in a cholesterol gene,” Musunuru said.

The nanoparticles are naturally absorbed by the liver, taking advantage of the liver’s job, which is to filter blood.

Once in the liver, the CRISPR components are released and begin to search for their target cholesterol gene, and switch it off.

In an early clinical study, a patient in his 20s with a severe high cholesterol condition saw his bad cholesterol rate drop by 60% and remain low for two years.

Statin medications are widely used to help control cholesterol and reduce the risk of heart disease. But research has found that people who are prescribed the medication after a heart attack often don’t stick with the drug, which must be taken daily.

What’s more, the treatment could one day be given to people who are known to be at high risk of developing heart disease, potentially avoiding a heart attack.

A two-hour infusion that eliminates the need for a daily medication could be especially beneficial in developing countries that lack access to healthcare or depend on outside sources to supply medications, since that supply can be unreliable.

Eli Lilly announced plans in June to acquire Verve for up to $1.3 billion.

Musunuru said he hopes the pharmaceutical giant’s support will accelerate the development of Verve’s cholesterol drug.

The drug is still years away from potentially becoming available. It needs more clinical testing to prove it is safe and effective, and must complete a rigorous regulatory approval process.

So far, researchers have had the most success using CRISPR to treat blood disorders (like sickle cell disease) or diseases associated with the liver. These are easy targets for CRISPR technology, since the therapies are infused into the bloodstream and are readily filtered by the liver.

The first Food and Drug Administration-approved CRISPR therapy for sickle cell disease works by turning off a gene that causes red blood cells to become misshapen.

Breast and ovarian cancers associated with BRCA gene mutations could be a potential next target.

Researchers have found that ovarian cancer typically begins in the fallopian tubes, which are relatively accessible organs because they are closer to the body’s surface. Breast cancer often begins in breast ducts, also close enough to the surface of the body.

Scientists are exploring whether a CRISPR solution injected directly into the fallopian tubes or breast ducts could potentially shut off the mutated gene before it causes cancer.

People with BRCA gene mutations have such a high risk of developing cancer that many preemptively opt to have their breasts or ovaries removed. Being able to “turn off” the cancer-causing gene could dramatically reduce their risk and the need for such drastic preventive measures.