Verve is harnessing advances in gene editing to develop single-course medicines to treat cardiovascular disease.
As humans, our DNA consists of a unique code that forms the building blocks for who each of us is as a person – defining key traits, including our health status.
Our DNA comprises four types of bases, referred to by specific letters, that spell out our unique genetic code. The four bases are adenine (A), cytosine (C), guanine (G) and thymine (T). These bases are present in our DNA as pairs.
Though our genome comprises more than 6 billion base pairs, a single misspelling in that code, known as a point mutation, can serve as the catalyst for serious illness. Through recent genetic discoveries, companies today are leveraging gene editing technologies to address these mutations and potentially cure the underlying cause of disease.
Gene editing has demonstrated incredible potential in driving new therapeutic breakthroughs to treat disease and continues to evolve. Gene editing works by making a permanent change in a target gene, disrupting the production of certain proteins that cause an underlying disease. Two common forms of gene editing are CRISPR-Cas9 and base editing.
CRISPR-Cas9 is the most prevalent form of gene editing technology today. Often called “genetic scissors,” CRISPR-Cas9 leverages a guide RNA (gRNA) to steer the Cas9 enzyme to the desired target DNA sequence where the mutation is located. It then activates the enzyme (the scissors) to “cut,” thus initiating the edit. This approach has limitations because it creates a double-stranded break in DNA and relies on cellular mechanisms to complete the editing process. CRISPR-Cas9 therapies can be effective, but they lack full control of the editing outcome, which can result in unwanted DNA modifications.
Newer gene editing approaches – such as base editing – can potentially address these limitations.
Base editing is a next-generation form of gene editing. Base editors can most simply be compared to pencils, in their ability to "erase" and rewrite a specific letter in a gene.
Base editing medicines comprise a messenger RNA (mRNA) and a gRNA, packaged in a delivery system – most often a lipid nanoparticle (LNP). The process works by binding a modified Cas9 protein to a gRNA, enabling direct targeting of a specific DNA sequence. Base editors are differentiated by the type of base editing enzyme – referred to as a deaminase – which carries out the chemical modification and is fused to Cas9.
