What if a heart attack and lifetime of statin drugs could be avoided with a onetime, two-hour infusion?<\/p>\n
Kiran Musunuru, a University of Pennsylvania<\/a> cardiologist and leading gene-editing researcher, thinks it\u2019s possible.<\/p>\n Musunuru cofounded Verve Therapeutics<\/a>, a company developing a therapy that uses gene editing to essentially turn off one of the liver genes that produces LDL, or bad cholesterol.<\/p>\n Eli Lilly<\/a> in June announced plans to acquire Boston-based Verve for up to $1.3 billion.<\/p>\n 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\u2019s.<\/p>\n 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\u2019s therapy.<\/p>\n The approach uses CRISPR, a gene-editing technology that allows scientists to alter DNA. It is named after a stretch of genetic code utilized \u2014 \u201cClustered Regularly Interspaced Short Palindromic Repeats.\u201d<\/p>\n 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. <\/p>\n Musunuru and colleagues at Children\u2019s 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<\/a>, who was born with a rare metabolic disorder that prevented him from processing protein. <\/p>\n \u00bb READ MORE: CHOP and Penn treated an infant with a rare disease by editing his genes<\/a><\/p>\n The Penn and CHOP team designed KJ\u2019s CRISPR treatment to find and correct a genetic misspelling in a liver enzyme.<\/p>\n Their success captured international attention for its potential to treat rare disorders. But Musunuru says CRISPR\u2019s potential is much broader.<\/p>\n Heart disease has become a leading cause of death, and Musunuru thinks it could be addressed with a two-hour CRISPR infusion.<\/p>\n \u201cWhy are we waiting for someone to have a heart attack?\u201d he said. \u201cWhat if you give them a onetime treatment and their cholesterol levels are permanently lower?\u201d<\/p>\n The Inquirer spoke to Musunuru about what\u2019s next for CRISPR technology. <\/p>\n How could CRISPR be used for heart disease?<\/p>\n The therapy embeds CRISPR components into lipid nanoparticles \u2014 essentially tiny soap bubbles \u2014 that are infused into the bloodstream. <\/p>\n The nanoparticles also contain mRNA<\/a>, 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.<\/p>\n \u00bb READ MORE: Penn scientists are honored for mRNA research used in COVID vaccines<\/a><\/p>\n \u201cWe give it a 20-letter address, the location in a cholesterol gene,\u201d Musunuru said. <\/p>\n The nanoparticles are naturally absorbed by the liver, taking advantage of the liver\u2019s job, which is to filter blood. <\/p>\n Once in the liver, the CRISPR components are released and begin to search for their target cholesterol gene, and switch it off. <\/p>\n 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. <\/p>\n What\u2019s the benefit of a one-and-done treatment for high cholesterol?<\/p>\n 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\u2019t stick with the drug, which must be taken daily.<\/p>\n What\u2019s 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. <\/p>\n 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. <\/p>\n What\u2019s next for Verve?<\/p>\n