Using the pathogenic prowess of viruses to benefit the medical field

Cara N. Wilder, Ph.D.

For over a century, viruses have captivated scientific minds. These agents of destruction are often considered the border between biochemistry and biology, not truly alive in the classical sense nor are they unorganized amalgamations of protein and DNA. In actuality, viruses are metabolically inert, ultramicroscopic organisms with the inherent ability to cause disease by invading host cells and hijacking replicative machinery. It is this natural infection process that not only fascinates contemporary scientists but has allowed them to develop exciting viral-based technologies, including novel drug delivery methods and vectored vaccines, for the advancement of disease treatment and prevention.

When creating viral nanoparticles, the genomic material is
removed from the viral head and replaced with drugs.
Photo: CDC/ Doug Jordan

Viral nanoparticles are viruses whose genomic material has been removed and replaced with therapeutic drugs. Because viruses have naturally evolved the ability to cross the host membrane, they are an ideal candidate for drug packaging and the targeted delivery to cancer cells. To minimize toxic side effects, infection, and induced immune response, human viruses are not used in the production of viral nanoparticles. Rather, these drug delivery systems are engineered from plant, insect, and animal viruses. Plant viruses, such as the Cowpea mosaic virus, are ideal candidates for nanotechnology as they are easy to produce in large quantities, can self-assemble around a nanoparticle, and hold a substantial volume of drugs.

One of the major benefits to using viral nanoparticles for drug delivery is that targeting molecules can be easily attached to the viral surface, allowing for the directed binding to cancer cells. This specific binding prevents the harm or death of surrounding healthy cells, thus reducing possible side effects. Though viral nanoparticles have the potential to be a beneficial treatment, there are several complications associated with their use as a drug delivery system including immune rejection and potential toxicity. Regardless, viral nanoparticles have the capability to revolutionize the treatment of disease, creating a safe and specific form of drug delivery.

In addition to functioning as a drug delivery method, viruses can also be employed as vectors for vaccines. Generally, vaccines are the most effective and inexpensive prophylactic tool for the prevention of disease. Viral-based vaccines are traditionally employed as live attenuated viruses or as chemically inactivated viruses. Though these types of preparations have been shown to induce protective immunity in animal models, mutations in attenuated viruses or incomplete viral inactivation poses a serious risk to those who are vaccinated. Recombinant vectored vaccines, however, offer a live-vaccine approach that does not employ the complete pathogen. Instead, genetic material from the microbial target strain is inserted into the genome of harmless viral strains, allowing for the safe expression of microbial antigens.

Vectored vaccines can constructed to protect against a
wide variety of microbial diseases.
Photo: CDC/ Doug Jordan

Newcastle disease virus (NDV), a negative-sense avian virus, is a common template used for the development of recombinant vectored vaccines. Not only does NDV grow to high titers in many cell lines and eggs, it can elicit a strong immune response in vivo, is harmless to humans, and is commercially available. Additionally, NDV replicates in the cytoplasm of infected cells, thus eliminating the problem of genetic integration. To create a viral vaccine vector from NDV, genes encoding foreign target proteins are inserted into the NDV genome through recombination. Upon vaccination with the live virus, the foreign target protein is expressed within the host cell cytoplasm where it is then available for processing by the cellular antigen-processing machinery for immune presentation. As a result, cellular immunity is activated and neutralizing antibodies are generated.

Overall, the ability of viruses to cause devastating epidemics has left them greatly feared by the human population. However, with contemporary technologies such as viral-based drug delivery systems and vectored vaccines, viruses can now be regarded as tools in disease treatment and prevention. Perhaps with further advancement in viral-based technologies and applications, scientists will be able to harness the full benefit of these organisms, improving life where there was once death.