Viral vectors

Viruses are infectious particles consisting of a nucleic acid (DNA or RNA) and a protein envelope. As they themselves do not have any metabolic processes, viruses reproduce by introducing their own genetic material into the cells of a host and manipulating the host cell to produce more viruses. 

Two types of viruses are particularly suitable for use in gene therapy studies: Retroviruses, such as alpha-retroviruses, gamma-retroviruses, spumaretroviruses or lentiviruses, integrate the transported genetic material directly into the genome of the target cell. Adeno- or herpes viruses, on the other hand, create an independent element outside the genome (episome), which is not replicated during cell division and is therefore lost after some time. 

Before a virus can be used as a vector, it must first be genetically modified so that no virus vector particles are formed after the genetic material is introduced (replication defective form). This is done by removing the corresponding viral sequences of the genetic material, so that only those for introducing and integrating the desired material into the genome of the target cell are preserved. 

The introduction of the gene-modified material into the target cell using viral vectors (transduction) can be performed either directly in the organism (in vivo) or on previously removed cells of the same (ex vivo). Although the latter has the advantage of excluding possible germline transmission, ex vivo gene therapy is limited to cells that can be relatively easily extracted from a patient's body and subsequently replicated. There is also the risk that reimplantation of the modified cells might be incomplete.

To assess the potency and safety of viral vectors, the number of infectious particles generated in the production process, the options for designing the particle surface for selective uptake into the respective target cells, the size and structure of the transferable gene-modified material, the possibility of eliminating virus-coding gene sequences, and the immunogenic or toxicological properties of the viral proteins required in the vector particle are of crucial importance. Furthermore, a previous infection of the patient with immunologically related viruses must be excluded in order to prevent an immune reaction.

Further information:

Baum, Christopher (2013):  Medizinisch-naturwissenschaftliche Aspekte. In: Baum, Christopher / Duttge, Gunnar / Fuchs, Michael: Gentherapie. Medizinisch-naturwissenschaftliche, rechtliche und ethische Aspekte. Bd. 15 der Reihe Ethik in den Biowissenschaften – Sachstandsberichte des DRZE. Freiburg i. B.: Verlag Karl Alber, 16–22.

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Illustration: 1. Collection of cells; 2. Modification of the virus; 3. Introduction of the desired genetic material; 4. Introduction the intact genetic material into the target cell using the virus; 5. Proliferation of cells with the corrected gene; 6. Infusion of the genetically modified cells; 7. The genetically modified cells produce the desired protein or hormones that could not be produced before. 

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Illustration: Viral vectors: Retroviruses and adenoviruses.

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