Reconstruction of the Oncolytic Maraba MG1 Virus from a Fully Synthetic DNA Genome

Abstract

Oncolytic viruses (OVs) are engineered to replicate selectively within cancer cells and destroy them while also inducing an immune response against the virus and the tumor. The Maraba MG1 strain is a double mutant of the Maraba virus that preferentially targets and kills cancer cells while minimizing harm to normal cells through interferon-dependent mechanisms. In preclinical tumor models, MG1 has demonstrated potent antitumor effects. Here, we demonstrate the feasibility of using synthetic DNA genome technology to engineer MG1 to develop a biosimilar oncolytic virus by modifying one of its commonly used restriction enzyme sites for an easy one-step cloning process. The ability to precisely modify the genome sequence of the virus allows greater control over its properties, and the simplified process of gene insertion accelerates the development of new therapies. Our platform will support the translation of this virus as a cancer treatment and provide a streamlined platform for personalized MG1 immunotherapy.