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07 May 2020

Virus-Inspired Science

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Today the words “virus” and “inspire” inevitably conjure up a negative connotation given the pandemic unleashed by the SARS-CoV-2 virus. Still, from the beginning of human existence, we have coexisted with millions of microorganisms that, in addition to representing a health risk, are also occasionally a scientific opportunity and essential weapons in the fight against specific illnesses, and they can even be crucial for the production of certain foods. Furthermore, microorganisms also develop energy and biotechnology processes that are invaluable for society.

For centuries humankind has been fighting the threat viruses represent to our health, but at the same time, our centuries-long bond with them means they have become a valuable source of information for science, technology, and even design. Peter B.Medawar, Nobel Laureate for Medicine in 1960 “for the discovery of acquired immunological tolerance,” was more simple and graphic in his description of viruses: they are “a piece of nucleic acid surrounded by bad news.” Although they have also had positive consequences for our planet. A curious example is the variety of colors that began to emerge in Dutch tulips in the early 16th century, a phenomena that was specifically caused by the tulip-breaking or mosaic virus which in turn resulted in “tulip mania” and what is generally considered to have been the first speculative bubble. In addition, many viral diseases only affect insects and are very selective in doing so; consequently, methods to convert insects into natural biological control agents are being investigated.

The film “Tulip Fever”(2017), inspired by a novel by Deborah Moggach and directed by Justin Chadwick is set in Amsterdam in the throes of tulip mania, when tulip bulb auctions hit exorbitant figures. Image: Ruby Films / The Weinstein Company / Worldview Entertainment

A Spanish Royal Academy of Sciences article explains the relatively late origin of virology, a young science constrained by the peculiarities the cultivation of a virus presents. These microorganisms can only reproduce if they infect other living cells, as opposed to bacteria, which is why in its early days this science turned to experimentation with animals and plants in order to reproduce viral diseases. Today, and under the right conditions, it is possible to cultivate entire viruses, recombinant viruses, or viral products in cells different to those of their natural hostos, as Mª Antonia Lizarbe explains in the cited article

Advancements in microbiology and technological tools that facilitate looking at the world on a microscopic levels are among the factors that have made it possible to identify the 219 virus species that are currently known to infect humans, according to a University of Edinburgh study. This fact, although it implies a risk to our health, also has an encouraging side for science: how to put these viruses to work for us?

A weapon against chronic, bacterial disease: gene therapy

Although living with hundreds of viruses is not good news, we shouldn’t lose sight of the medical and scientific potential these fascinating microorganisms represent. Research on the mechanisms that unleash viral diseases has contributed to the development of innovative treatments and diagnostic approaches based on genetic engineering and molecular biology, which redirect the potential of the virus’ replication and communication mechanism so it works on our behalf. What the research is essentially trying to do is to hack into the virus itself.

Herpes virus image under the microscope, taken by Dr. Fred Murphy, Sylvia Whitfield, USCDCP / Image: public domain (CC0)

Viruses: the safest genetic messengers

In the case of gene therapy, viruses are modified to be used as vectors (transmission vehicles) in order to introduce modified genetic material with therapeutic properties into specific target cells. Lentiviral vectors (LVs), for example, have been designed for gene therapy and have proven to be promising. Thanks to advances in design and large-scale production, LVs have become the safest and most effective gene delivery systems, as explained by several researchers in the publication Current Opinion in Molecular Therapeutics. Treating infections and genetic diseases with these “hacker” viruses has been under investigation since 2002. To make it to work, part of its genetic data (genome) is canceled, so that it is prevented from multiplying within the cell. Some LVs are derived from herpes simplex, for example.

“Smart” viruses to attack bacteria and administer medication

Viruses that can infect bacteria are called phage (or bacteriophage) and are also being studied specifically to treat bacterial infections, since their main advantage is that they are activated by the bacteria, but remain dormant in our eukaryotic cells, as explained by research conducted at the Kochi Medical School in Japan.

Viruses are also proving promising in diagnostic medicine. In the hopes of developing a less invasive technique than biopsy or surgery, researchers at the Scripps Research Institute in the United States have turned to nanotechnology to design virus-based nanoparticles (VNP) that will facilitate post cancer treatment or cardiovascular disease follow-ups using imaging. Included among the different nanoparticles are dendrimers, liposomes, and paramagnetic nanoparticles, among others.

These “smart and mutant” viruses assume various functions such as the administering pharmaceuticals and targeted delivery, which means they have huge potential to make therapies increasingly specific. VNPs, viruses transformed into nanosystems, are designed to locally distribute the chemical substances that are used as treatments in order to adjust the treatment concentration levels to the disease focal point, thus helping reduce adverse secondary effects in addition to facilitating early detection of disease.

Oncolytic viruses: cancer-curing mutant viruses

Using viruses to destroy tumors, a process known as viral oncolysis, dates back to early 1900. However, it has only been in recent decades that oncolytic virus therapy has emerged as a promising approach in the fight against cancer.

The conceptual basis of this process lies in viral particles that have been genetically attenuated so that they will only remove the malignant cells (the tumor) and leave the healthy cells alone. Oncolytic viruses are able to recognize and infect or injure the tumor cells. As a group of researchers at the University of South Paris explain, research has even gotten so far as to suggest an improvement in the oncolytic activity of these viruses that consists of introducing suicide genes into the viral genome.

The medical community is also taking advantage of viral disease mechanisms, using these biological routes in the fight against other diseases. Researchers at the University of Queensland have developed a “polymer based vehicle” that limits the flu virus’ escape mechanism and in addition is programed to liberate RNA (genetic data) that interferes in the intracellular liquid. It thereby represents a technique with potential for treatments that require multiple, repeated doses over a longer period of time. 

Dory Gascueña López for OpenMind


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