Synthetic viruses: How far can we go?

Advances in molecular biology, DNA synthesis, and computational design have made it possible to build viruses from written genetic sequence alone, without a natural template. Since the first chemical synthesis of an infectious poliovirus genome in 2002, synthetic virology has produced steadily larger and more complex genomes, reconstructed extinct pandemic viruses for research, and assembled a live orthopoxvirus from mail-order DNA fragments. In parallel, the same underlying toolkit, virus reverse-genetics systems, genome and gene synthesis, and increasingly artificial intelligence-guided sequence and protein design, has produced major public health benefits, including messenger RNA and self-amplifying RNA vaccines, oncolytic virotherapies and engineered gene therapy vectors. This review surveys the history, enabling technologies, and current capabilities of synthetic virology; describes its principal applications in vaccinology, oncology, and gene therapy; and examines the dual-use biosecurity risks this capability creates, including gain-of-function research, the declining cost and increasing accessibility of gene synthesis, and the emerging challenge of AI-designed sequences evading biosecurity screening. It then reviews the governance landscape, including dual-use research of concern oversight, nucleic acid synthesis screening, and international coordination efforts, before considering how far the field can and should go, and what adaptive governance would be required to keep pace with it.