Viral Vectors for Gene Delivery

To overcome the limitations of their small genomes, viruses have evolved to co-opt the gene expression mechanisms of infected host cells. This makes them ideally suited as delivery vectors, both for scientific research and for clinical applications.

Viruses are simple particles, consisting of a genome inside a protein shell (the capsid), which may additionally be surrounded by a lipid bilayer (the envelope). The genetic material is either DNA or RNA, which may be either double-stranded (ds) or single-stranded (ss). In order to replicate, each single virus particle (virion) must infect a suitable host cell. Infection is commonly achieved through receptor binding, although enveloped viruses are capable of direct fusion owing to the viral envelope being derived from the host cell membrane. Once inside the host cell, the virion replicates by hijacking the host’s cellular machinery. Large numbers of viral particles are then released, either via lysis (non-enveloped viruses) or budding (enveloped viruses), generally killing the host cell in the process. Although many viruses are harmless, pathogenic examples include the Orthomyxoviridae family, which encompasses the influenza A and B viruses; the Coronaviruses, such as SARS-CoV-2; and the Papillomaviridae family, which can lead to cancers. Viral vectors are viruses that have been genetically engineered to prevent them from replicating in host cells. Specifically, the genes encoding the proteins necessary for replication are removed and the virus is modified to contain a gene for a desired payload. For viral vectors to replicate, they are typically introduced into host cells with one or more helper plasmids, which encode various replication and packaging components. Viral vectors have broad utility, spanning basic research into gene function through to advanced cell and gene therapy applications.