HQ Team
October 27, 2024: A clinical-stage US gene-editing company, Precision BioSciences, got approval from the Eastern European country of Moldova to start an in vivo human trial of a therapy to treat chronic hepatitis B.
The clinical trial application got the nod from Moldovian authorities, and the Durham, North Carolina-based company has opened the first-stage experiments of dosing the patients, according to a statement.
The in vivo process involves gene editing inside the human body and is the opposite of in vitro or external, say, in a laboratory.
The therapy is engineered to target the hepatitis B virus (HBV) genome and drive functional cures for patients with chronic forms of the disease.
The precise gene editing tool cuts a highly conserved sequence in the hepatitis B viral genome and is designed to eliminate cccDNA and inactivate integrated HBV genomes.
cccDNA
The cccDNA (covalently closed circular DNA) is a special DNA structure that arises during the propagation of some viruses in the cell nucleus and may remain permanently there.
Precision BioSciences showed preclinical data demonstrating the ability of its gene-editing platform to achieve “high-efficiency gene insertion, gene replacement and base correction via homology-directed repair.”
The data was presented at the European Society of Gene & Cell Therapy 31st Annual Congress held between October 22-25, 2024, in Rome, Italy.
Scientists demonstrated how the new technology of the company, called Arcus, inserted genes into cells. This method successfully inserted genes in over 85% of T cells (a type of immune cell) and 39% of liver cells that do not divide.
The success rate is mainly due to a process called homology-directed repair or HDR, which requires specific DNA sequences to guide the insertion.
Restore function
The technology scores over others because it can make a wide variety of genetic changes—unlike other gene-editing technologies that are limited to just a couple of changes.
Arcus can create all twelve possible types of base changes in DNA and can also remove or add specific bases. Moreover, it can insert entire genes or replace large parts of existing genes, which is crucial for restoring their function.
“Gene editing enzymes that support efficient HDR are relatively rare,” said Jeff Smith, PhD, Co-Founder and Chief Research Officer of Precision BioSciences.
“However, we demonstrate here that ARCUS is capable of utilising HDR with high efficiency to achieve a range of gene editing outcomes, including specific base changes, insertions, and the replacement of large segments of DNA within the genome.”
300 million people
Michael Amoroso, Chief Executive Officer of Precision BioSciences said the study aimed to generate important clinical safety and efficacy data to bring a potentially curative treatment to the nearly 300 million patients living with chronic hepatitis B globally.
Precision has submitted multiple global clinical trial applications as part of its global Phase 1 regulatory strategy.
Hepatitis B is a leading cause of morbidity in the US and death globally, with no curative options currently available for patients. In 2019, despite the availability of approved antiviral therapies, an estimated 300 million people globally and more than 1 million people in the US were estimated to have chronic hepatitis B infection.
An estimated 15% to 40% of patients with HBV infections may develop complications, such as cirrhosis, liver failure, or liver cancer (hepatocellular carcinoma), which account for the majority of HBV-related deaths.
