Gene Editing Takes a Major Step Forward in Tackling Cardiovascular Disease

On July 13, 2022, a volunteer in New Zealand became the first patient in the world to undergo gene editing to lower "bad" cholesterol. According to an article in MIT Technology Review, this important development not only signals the future of using gene editing technology to prevent cardiovascular disease, the world's "biggest killer," but also represents an important step forward in the use of CRISPR-based gene editing technology to treat common diseases.

Cardiovascular disease is the leading cause of death worldwide. However, while it is well documented that many cardiovascular diseases can be prevented, it is not easy to prevent them before they occur.

Take for example the reduction of low-density lipoprotein cholesterol (LDL-C), also known as "bad" cholesterol, whose high levels are a major contributor to cardiovascular disease. While diet control and exercise can be effective in lowering LDL-C levels, most people are not able to follow this lifestyle rigorously on a consistent basis. Although oral statins and innovative therapies such as weekly, monthly, or even semi-annual injections have been introduced, innovative therapies are not yet widely available, and medication adherence is another major challenge in the management of cardiovascular disease.

In this study, patients received a gene editing therapy that uses a single-base editor modified by a CRISPR-based system to alter a single letter of the PCSK9 gene in patient cells to achieve the effect of inactivating PCSK9, a popular target for LDL-C reduction, and the efficacy of inhibiting its activity has been validated by several FDA-approved therapies.

The clinical trial will examine the safety and efficacy of a single-base editing therapy called VERVE-101 in 40 patients with heterozygous familial hypercholesterolemia (HeFH), with preliminary clinical data from the trial expected to be reported next year. If the trial results are positive, it is expected to open the door to the use of single-base gene editing therapy in the prevention of cardiovascular disease in a broad range of populations.

Currently, most gene therapies target rare diseases with small patient populations, and the use of gene editing technology for common diseases requires overcoming multiple challenges, such as the safety of the therapy, where controlling the off-target effects of gene editing is critical.

In contrast to CRISPR technology, single-base editing enables precise gene editing without cutting the DNA double strand. If CRISPR-Cas9 technology is the "scissors" that modifies the genome, then single-base editing is the "pencil and eraser" that erases and rewrites a letter in a gene. Theoretically, it could reduce off-target effects and lead to a higher safety profile.

In addition, the study uses lipid nanoparticles (LNP) as a vector for delivering single-base editing therapies. Unlike viral vectors commonly used in gene therapy, LNP-delivered single-base editing therapies are only transiently present in humans, further reducing the risk of off-target single-base editing.

Single treatment and permanent cure are the expectation of patients and the pursuit of researchers. In recent years, the rapid progress of gene therapy, cell therapy, and CRISPR gene editing therapies has brought hope to treat intractable diseases from the root cause. It's expected that the clinical development of single-base editing technology goes well and brings more one-time cure therapies to the patients soon.

Candy Swift: Focus on the cutting edge biological information around the world.