The choice of vector, target cell and protocol used will depend upon a number of considerations. The major consideration is obviously what the ultimate goal of the gene therapy treatment is in any given case. For example, in some instances it may be to correct an inherited genetic defect, whereas in other instances it may be to confer a novel function upon the recipient cell. An example of the former would be the introduction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (the cystic fibrosis gene) into the airway epithelial cells of cystic fibrosis sufferers. An example of the latter would be the introduction of a novel gene into white blood cells whose protein product is capable of in some way interfering with HIV replication. Such an approach might prove an effective therapeutic strategy for the treatment of AIDS.
An additional consideration that may influence the protocol used is the desired duration of subsequent expression of the gene product. In most cases of genetic disease, long-term expression of the inserted gene would be required. In other instances (e.g. some forms of cancer therapy or the use of gene therapy to deliver a DNA-based vaccine), short-term expression of the gene introduced would be sufficient/desirable.
For most applications of gene therapy, straightforward expression of the gene product itself will suffice. However, in some instances, regulation of expression of the transferred gene would be required (e.g. if gene therapy combating insulin-dependent diabetes mellitus was to be considered). Achieving such expressional control over transferred genes is a pursuit that is only in the early stages of development.
The choice of target cells is another point worthy of discussion. In some instances, this choice is predetermined, e.g. treatment of the genetic condition, familial hypercholesterolemia, would require insertion of the gene coding for the low-density lipoprotein receptor specifically in hepatocytes.
In other cases, however, some scope may be available to choose a target cell population. Even in the case of redressing some genetic diseases, it may not be necessary to correct genetically the exact population of cells affected. For example, a hallmark of several of the best characterized genetic diseases is the exceedingly low production of a circulatory gene product. Examples include clotting factors VIII and IX, a lack of which leads to haemophilia. It may be possible to correct such defects by introducing the appropriate gene into any recipient cell capable of exporting the gene product into the blood. Is such cases, choosing a target cell could be made upon practical considerations, such as their ease of isolation and culture, their capacity to express (and excrete) the protein product, and their half lives in vivo.
Several cell types, including keratinocytes, myoblasts and fibroblasts, have been studied in this regard. It has been shown, for example, that myoblasts, into which the factor IX gene and the growth hormone gene have been introduced, could express their protein products and secrete them into the circulation.
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