A biotech company is utilizing this platform to rid people of the virus using a technology that differs from CRISPR-Cas9.
For the uninitiated, gene (genome) editing “is the process of modify genes of living organisms to improve our understanding of gene function and develop ways to use it to treat genetic or acquired diseases.”1
Currently, gene editing therapies are being studied for a whole host of diseases and chronic conditions including cancer, diabetes, AIDS, hemophilia, and others. This type of therapy has not been FDA approved yet for any diseases, but for all involved or understand the technology, there is a great deal of promise.
Looking at chronic conditions, people are often being treated with multiple therapies and have to deal with side effects and other quality of life issues that could lead to more severe health issues because of the nature of living with such conditions over many years. For example, chronic hepatitis B can require indefinite treatment, and some people do have medication side effects, or in severe cases, the condition can lead to liver issues.
Some in the medical industry believe chronic HBV would be an ideal target for gene editing therapies.
“A number of genetic conditions or even infectious diseases like hepatitis B [have] the root cause within your DNA,” Cassandra Gorsuch, PhD, head of Gene Therapy Discovery, Precision BioSciences, said. "And most of our treatment options across the board treat symptoms of diseases but not the actual causes of diseases. The idea of gene editing approach is to use different types of technologies to permanently alter the DNA sequence, which is the underlying cause of disease.”
Gorsuch’s company is a clinical stage biotechnology company that has created its novel and proprietary genome editing platform, ARCUS. This platform is being developed for use in DNA genome insertion, deletion, and repair. Specifically, their PBGENE-HBV product gene editing candidate uses a lipid nanoparticle (LNP) delivery of ARCUS mRNA. (See illustration above.)
Data from Precision’s preclinical study demonstrated ARCUS targeted and degraded HBV covalently closed circular (cccDNA) by 85% and reduced expression of HBV’s Surface Antigen (HBsAg) by 77% in HBV-infected primary human hepatocytes (PHH). The cccDNA plays a central role in chronic HBV.
Similar levels of editing were achieved in novel mouse and NHP models following its LNP delivery resulting in a 96% reduction in HBsAg.
Although this is early in the development process, the company plans to move forward with PBGENE-HBV, and they will file for an FDA investigational new drug application in 2024.
Gorsuch spoke to Contagion about this gene editing candidate, how their platform differs from other technologies such as CRISPR/Cas9, and the company’s hopes for its potential place in the market for HBV treatment.
1. Gene Editing – Digital Media Kit. National Institutes of Health. Updated November 5, 2020. Accessed August 29, 2022. https://www.nih.gov/news-events/gene-editing-digital-press-kit