Recent genetic discoveries and increasing sophistication of gene editing technologies have together aligned to produce a transformative moment in the scientific approach to coronary heart disease.
Genetic studies have revealed naturally occurring gene variants that dramatically lower some individuals’ lifetime risk of coronary heart disease and protect against heart attack. Gene editing offers the transformational possibility of developing medicines that confer protective variants to adults with coronary heart disease.
Overview of Gene Editing
In recent years, gene editing has demonstrated incredible potential to drive new therapeutic breakthroughs to treat disease. Using gene editing, Verve aims to develop medicines, administered once in life, that mimic naturally protective gene variants and safely turn off a target gene in the liver to permanently lower LDL cholesterol or triglyceride levels and thereby treat coronary heart disease in adults.
Variants in a number of genes, all expressed in the liver, have been found to be associated with reduction of risk of coronary heart disease. For example, individuals who have variants that inactivate the PCSK9 gene have lower levels of cholesterol, are protected from heart attack, and are otherwise healthy. These genes are well-characterized and highly validated targets for gene editing.
Heterozygous null mutations in the PCSK9 gene, occurring in about 1 in 40 individuals of African ancestry, leads to lifelong lower LDL (low-density lipoprotein) cholesterol and 80% lower risk of heart attack.
Our Mechanism of Action
Our gene editing medicine is comprised of a messenger RNA (mRNA) and a guide RNA (gRNA) packaged in a lipid nanoparticle (LNP); the medicine precisely edits and permanently turns off a target gene in the liver using base editing to make a single spelling change in DNA. Learn more about the mechanism of action for our lead product candidate, VERVE-101, which uses adenine base editing to knock out the PCSK9 gene to permanently lower blood levels of LDL cholesterol (LDL-C) and treat coronary heart disease (CHD):
Our Ethical Commitment
As we advance in our mission to develop medicines for adults with coronary heart disease, Verve will work in a manner that is consistent with the ethical and scientific frameworks set forth by leading professional societies, regulators, and biomedical ethicists.
All of the medicines to be developed by Verve involve making edits in adult (somatic) cells, which are not passed down to offspring. We will not edit embryos, sperm cells, or egg cells.
Safety is paramount for Verve. We will be implementing a rigorous safety protocol with the best available technology for detecting off-target effects. Verve has one of the world-leading experts on gene editing safety on our team, and our clinical development plan will proceed responsibly and transparently.