Viruses have always seemed like a danger to human health. From the spanish flu to SARS-CoV-2, viruses have caused global panic and pandemics. Viruses may have the chance to be an unlikely hero as medical professionals expand their potential to transport therapies to specific tissues.
History of Viral Treatment for Cancer
In the 1950s, doctors observed that unrelated viral infections correlate with cancer patients that show signs of improvement. Further research showed that viruses could destroy tumors. The earlier observations led to an explosion in the study of oncolytic viruses, or viruses that infect and kill cancer cells. One of the major concerns with these types of viruses is their selectivity to cancer cells versus healthy cells. Through genetic modification, these viruses can be altered to infect and proliferate in cancer cells more successfully than in healthy cells. Oncolytic viruses infect cells, but selectivity replicates in tumor cells. Rapid replication of viruses within these cells cause the cell to burst. The release of the virus also indicated to the immune system to activate macrophages in search of cancer cells.
The study of viruses started in the 1950s, but it became more popular in the 1990s when more modern genetic editing techniques allowed scientists to control for severity, spread, and proliferation of the virus. The uses of viruses in cancer treatment is early in development, but the first approved viral treatment for melanoma in 2015. Hopefully, these oncolytic viruses will prove useful in destroying cancerous tumors in areas where mechanical treatment is dangerous.
Selecting a Virus Type
There are also a number of viruses that vary in structure, DNA capacity, and integration type. One key to successful viral therapies is to choose the optimal virus to use. The variations between virus types is due to differences in their structure. For example, herpesviridae is very large and can contain almost four times the genetic information that papovaviridae can. However. herpesviridae has a more difficult time diffusing through areas and tissues. Since herpesviridae is also enveloped, it is more likely to cause an immune response detrimental to its therapeutic objective. Viral variation is also a factor of the type of genetic information that the virus carries. This can affect how long the foreign sequence affects the cell. In herpesviridae, the genetic information is stored as double-stranded DNA, and this requires the sequence to enter the nucleus and integrate with the host genome. As a result, the introduced sequence remains in the host cell and affects expression for a relatively long period of time. Whereas, viruses that store information as single-stranded RNA can affect expression by its presence in the cytoplasm, and it has shorter effects on the host.
One of the viral types that has recently become popular for studying therapeutic potential is the adeno-associated virus, which is a part of the parvoviridae family. Compared to other viruses, the adeno-associated virus has less of a risk of disease infection and causing an immune response. This could also allow a high dose of adeno associated viruses to be used compared to other types.
As mentioned, the potential of viral therapies and the research into this field expanded in the 1990s when gene editing became a realistic procedure. Since then, biologists have been exploring using genetic editing for anything from blocking expression of certain genes to adding a completely new sequence into the genome. In terms of viral therapy, gene editing can allow scientists to selectively modify the viral genome. These modifications can remove the negative immune responses associated with a virus, allow the virus to target specific tissues or areas of the body, and alter the replication rate of the virus depending on the environment it’s in.
Depending on what the scientist is trying to alter, there may not be a known sequence to add or remove to get their desired result. One solution is to modify the genome through directed evolution. This process involves randomly altering a portion of the genome which is associated with what you want to change. If they want to allow the virus to cross the blood brain barrier, then there are sequences that are known to affect the viral envelope. After creating a mutant library of this sequence, the virus is incubated in a similar environment to the one you want it to successfully function in. The viruses undergo testing for correct function, and the process is repeated until a satisfactory virus is produced. The desired mutation can be incorporated into the therapeutic viral treatment to acquire the desired results.
Future of Viral Therapy
Viral therapy has already shown to be a possible treatment in destroying cancerous tumors, and it is likely that these breakthroughs could lead to tumor removal across the body instead of just the approved treatment for skin cancer. There is also potential for viral therapies to be effective in a range of diseases. Viruses are a natural transport system that can be specified to target only certain tissues. Viruses are also unique in that they can integrate DNA or RNA sequences into a cell and establish expression for foreign sequences. These characteristics have led scientists to propose viral therapy for transport in the body and integration of genetic sequences. One current study is the ability of viral therapy to slow or reverse the progression of Parkinson’s disease through triggering the release of dopamine. Overall, viruses have gone from some of the most dangerous pathogens to a potential aid against disease.