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Antisense RNA

Retroviral therapy

This specific kind of retroviral therapy is type specific in that it targets only single stranded RNA viruses, and though there is limitation it is effectively a very simple and powerful therapeutic agent. At the heart of the treatment is to use an infectious particle whose payload can only be activated in RNA virus infected cells because for activation the therapy requires a specific gene product of the virus.

            RNA viruses have a genome composed from, as their name suggests, RNA, this is not the usual genetic material, all of our cells use DNA as the genetic template, and these sets are transcribed to RNA before the instructions are translated into protein. RNA viruses get round this orderly sequence of operations, the central dogma, by reverse transcribing their RNA back into DNA, which is then stabilised and is used to transcribe the gene products encoded within their genome. Without this ability to reverse transcribe the virus can not function, and it relies on the protein that performs this function, reverse transcriptase.

            Because only cells with viral infection will have reverse transcriptase (as it is not part of the genome) this provides a powerful selection agent for a RNA virus therapy. There are many genes that encode a dangerous product, potent enough to destroy the cell, but a DNA based vector could initiate the destruction of healthy cells, yet alone infected ones, so instead of writing this lethal message on a DNA strand, it is instead written on an RNA one. The dangerous gene and its promoter are written in the reverse sense, and are flanked on either side by terminal repeats the remains of the original RNA vector, these repeats are also used in the therapy to stabilise the reverse transcribed DNA by circularisation. Also in addition to the repeats there are region complimentary to the original pathogenic virus whose function is described later. The infectious particles are packaged by helper cell lines which have been transfected with the modified vector.

            The infectious particles are generally adapted to target the same cells as the original RNA virus, this is in most simply achieved by using the original pathogenic wildtype and stripping out all genetic material apart from the coat proteins, which give a virus its specificity for cell type.

            When one of these particles infects an already infected cell the liberated RNA can bind to the original viral RNA through its complimentary sequence. The short region of duplex RNA creates a primer for the reverse transcription of the rest of the RNA genome. When the reverse transcription process is complete the DNA duplex circularises and the lethal gene can begin to be transcribed. Only when the DNA version is produced can the lethal gene product be generated, as even if the original RNA as translated it would generate a nonsense gene product as it is in the wrong sense, thus the fatal gene product can only be generated in RNA virus infected cells.

            This kind of therapy was used in addition to other advanced retroviral therapies (ARTs), though its relative simplicity and its non replicating nature required repeated rounds of treatment, it illicited very few complications in its use. Like the other ARTs it was developed in the golden age of biotechnology at the beginning of the 21st century, though because of its relatively limited abilities and targets it has not been greatly redesigned since the first forms.
 

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