Engineering Virus Capsids Into Biomedical Delivery Vehicles: Structural Engineering Problems in Nanoscale

Virus capsids have evolved to protect the genome sequestered in their interior from harsh environmental conditions, and to deliver it safely and precisely to the host cell of choice. This characteristic makes them naturally perfect containers for delivering therapeutic molecules to specific locations. Development of an ideal virus–based nano-container for medical usage requires that the capsid be converted into a targetable protein cage which retains the original stability, flexibility and host cell penetrating properties of the native particles, without the associated immunogenicity, and is able to encapsulate large quantities of therapeutic or diagnostic material. In the last few years, several icosahedral, non-enveloped viruses, with a diameter of 25–90 nm—a size which conveniently falls within the 10–100 nm range desirable for biomedical nanoparticles-have been chemically or genetically engineered towards partial fulfilment of the above criteria. This review summarizes the approaches taken towards engineering viruses into biomedical delivery devices and discusses the challenges involved in achieving this goal.