Genetically modified virus

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A genetically modified virus is a

Genetically modified viruses are generated through genetic modification, which involves the directed insertion, deletion, artificial synthesis, or change of nucleotide sequences in viral genomes using biotechnological methods. While most dsDNA viruses have single monopartite genomes, many RNA viruses have multipartite genomes, it is not necessary for all parts of a viral genome to be genetically modified for the virus to be considered a genetically modified virus. Infectious viruses capable of infection that are generated through artificial gene synthesis of all, or part of their genomes (for example based on inferred historical sequences) may also be considered as genetically modified viruses. Viruses that are changed solely through the action of spontaneous mutations, recombination or reassortment events (even in experimental settings), are not generally considered to be genetically modified viruses.

Viruses are generally modified so they can be used as vectors for inserting new genetic information into a host organism or altering its preexisting genetic material. This can be achieved in at least three processes :

1. Integration of all, or parts, of a viral genome into the host's genome (e.g. into its chromosomes). When the whole genetically modified viral genome is integrated it is then referred to as a genetically modified provirus. Where DNA or RNA which that has been packaged as part of a virus particle, but may not necessarily contain any viral genes, becomes integrated into a hosts genome this process is known as transduction.
2. Maintenance of the viral genome within host cells but not as an integrated part of the host's genome.
3. Where genes necessary for genome editing have been placed into the viral genome using biotechnology methods,^[1] editing of the host's genome is possible. This process does not require the integration of viral genomes into the host's genome.

None of these three processes are mutually exclusive. Where only process 2. occurs and it results in the expression of a genetically modified gene this will often be referred to as a transient expression approach.

The capacity to

In 1972, the earliest report of the insertion of a foreign sequence into a viral genome was published, when Paul Berg used the EcoRI restriction enzyme and DNA ligases to create the first ever recombinant DNA molecules.^[5] This was achieved by joining DNA from the monkey SV40 virus with that of the lambda virus. However, it was not established that either of the two viruses were capable of infection or replication.

In 1974, the first report of a genetically modified virus that could also replicate and infect was submitted for publication by Noreen Murray and Kenneth Murray.^[6] Just two months later in August 1974, Marjorie Thomas, John Cameron and Ronald W. Davis submitted a report for publication of a similar achievement.^[7]

Collectively, these experiments represented the very start of the development of what would eventually become known as biotechnology or recombinant DNA methods.

Health applications

Gene therapy

Gene therapy^[8] uses genetically modified viruses to deliver genes that can cure diseases in human cells.These viruses can deliver DNA or RNA genetic material to the targeted cells. Gene therapy is also used by inactivating mutated genes that are causing the disease using viruses.^[9]

Viruses that have been used for gene therapy are,

Another potential use of genetically modified viruses is to alter them so they can directly treat diseases. This can be through expression of protective proteins or by directly targeting infected cells. In 2004, researchers reported that a genetically modified virus that exploits the selfish behaviour of cancer cells might offer an alternative way of killing tumours.[17]^[18] Since then, several researchers have developed genetically modified oncolytic viruses that show promise as treatments for various types of cancer.^{[19] [20] [21][22][23]}

Vaccines 

Most

Genetically modified viruses that make the target animals infertile through immunocontraception have been created^[33] as well as others that target the developmental stage of the animal.^[34] There are concerns over virus containment^[33] and cross species infection.^[35]

Trees

Since 2009 genetically modified viruses expressing spinach defensin proteins have been field trialed in Florida (USA).^[36] The virus infection of orange trees aims to combat citrus greening disease, that had reduced orange production in Florida 70% since 2005.^[37] A permit application has been pending since February 13, 2017 (USDA 17-044-101r) to extend the experimental use permit to an area of 513,500 acres, this would make it the largest permit of this kind ever issued by the USDA Biotechnology Regulatory Services.

Insect Allies program

In 2016

Concerns have been expressed about how this program and any data it generates will impact biological weapon control and agricultural coexistence,[45]^[46][47] though there has also been support for its stated objectives.^[48]

Technological applications

Lithium-ion batteries

In 2009, MIT scientists created a genetically modified virus has been used to construct a more environmentally friendly lithium-ion battery.^[49][50][51] The battery was constructed by genetically engineering different viruses such as, the E4 bacteriophage and the M13 bacteriophage, to be used as a cathode. This was done by editing the genes of the virus that code for the protein coat. The protein coat is edited to coat itself in iron phosphate to be able to adhere to highly conductive carbon-nanotubes. The viruses that have been modified to have a multifunctional protein coat can be used as a nano-structured cathode with causes ionic interactions with cations. Allowing the virus to be used as a small battery. Angela Blecher, the scientist who led the MIT research team on the project, says that the battery is powerful enough to be used as a rechargeable battery, power hybrid electric cars, and a number of personal electronics.^[52] While both the E4 and M13 viruses can infect and replicate within their bacterial host, it unclear if they retain this capacity after being part of a battery.

Safety concerns and regulation

Bio-hazard research limitations

The National Institute of Health declared a research funding moratorium on select

A scientist claims she was infected by a genetically modified virus while working for Pfizer. In her federal lawsuit she says she has been intermittently paralyzed by the Pfizer-designed virus. "McClain, of Deep River, suspects she was inadvertently exposed, through work by a former Pfizer colleague in 2002 or 2003, to an engineered form of the lentivirus, a virus similar to the one that can lead to acquired immune deficiency syndrome, or AIDS."^[59] The court found that McClain failed to demonstrate that her illness was caused by exposure to the lentivirus,^[60] but also that Pfizer violated whistleblower protection laws.^[61]

References