What’s the problem?  Viruses are essential tools in modern biotechnology, with applications in cancer immunotherapy, gene therapy, and vaccine development. However, producing viruses efficiently at clinical and commercial scale remains a major bottleneck. Many commonly used human cell lines, including the widely adopted A549 line, retain natural antiviral defense mechanisms that limit viral replication, resulting in lower yields and increased manufacturing costs.  One key antiviral factor is the human protein SAMD9, which restricts viral replication inside host cells. Its presence significantly reduces the efficiency of producing certain therapeutic viruses, including oncolytic viruses such as myxoma virus. This limitation slows research, clinical development, and commercialization of promising viral therapies.  What does this technology do?  This patent covers engineered human cell lines modified to eliminate or reduce expression of the antiviral host factor SAMD9, enabling significantly enhanced viral replication in vitro. By removing this natural antiviral restriction, the modified cells allow viruses to replicate more efficiently, increasing overall production yields.   The technology can be implemented using gene-editing approaches such as CRISPR-Cas9 to generate stable, virus-permissive cell lines suitable for research, clinical development, and manufacturing. These engineered cells have demonstrated improved production of oncolytic viruses, which are increasingly used as targeted cancer therapeutics and immunotherapies.  By improving viral replication efficiency, this innovation has the potential to:  This platform provides a practical and scalable solution for enhancing viral production using human cell lines compatible with therapeutic applications.  Inventor  Jia Liu, PhD, Associate Professor in the Department of Microbiology and Immunology at University of Arkansas for Medical Sciences (UAMS).