## Viruses are capable of DNA transfer

In the case of hereditary diseases, medical interventions are largely limited to prevention and treatment of symptoms, rather than addressing the cause of the disease, namely the mutated DNA. A key discovery that led to the development of therapies for inherited diseases was the discovery of transduction, a transmission of DNA by viruses, in the early 1950s. Bacteria-infecting viruses, called bacteriophages, have been shown to be able to transfer heritable traits from one bacterium to another. Several traits could be transferred using bacteriophages, such as the ability to grow on different substrates, fermentation as a source of energy, or resistance to certain antibiotics. In this process, the virus injects its own DNA into the bacterium after contact with the cell. The viral DNA is replicated, resulting in many copies of it in the cell. At the same time, the protein components of the viral envelope, called capsid, are produced by the bacteria. The viral DNA is packaged into the capsid, and the viral particle, virion, is completed. A necessary step prior packaging into the protein particle is cutting the viral DNA to a suitable size. During this process, fragmentation (cutting into smaller pieces) of the bacterial DNA also occurs. In rare cases, this may result in the bacterial DNA fragment being packaged into the newly formed capsid instead of the viral nucleic acid. After bacteriophage progeny assembly, the host cell bursts and the released virions can infect other bacteria. Depending on the information contained in the bacteriophage, an infected bacterium may permanently acquire a new trait after the incorporation of foreign DNA into its genome (Figure 10.1).

The discovery that DNA can be transferred between cells by viruses and subsequently inserted into the host genome was revolutionary. If such transfer is possible in bacteria, surely there must be viruses that can do the same in humans. Indeed, retroviruses such as HIV (human immunodeficiency virus) are able to insert their genetic information into the genome of the host and then force the cell to express their genes (Figure 10.2). Of course, the use of the HIV virus in medicine would be extremely dangerous, but mankind has several methods by which the viral DNA or RNA can be manipulated so that the originally dangerous virus becomes much safer. To do this, the genes whose products ensure the replication and capsid formation are removed from the genome of the virus. A virus modified in this way can infect the host cell, but is unable to replicate and spread further. In addition, the vacated space in the virions can be filled, for example, by a healthy human gene that we want to transport into the cell and potentially repair the mutated one. However, a major risk in using viruses that are able to insert their genetic information into the host DNA is their poor targeting. It is very important to know where the therapeutic DNA will be inserted. For example, the insertion could disrupt a gene that is important for regulating cell division, potentially triggering tumour transformation of the cell.