The three scientists contend that, while the prion hypothesis is not universally accepted, prions nevertheless may be gatekeepers controlling disease susceptibility. At the other extreme, prion proteins serve as the prototype for a new class of infectious pathogen and establish protein misfolding as a novel mechanism of disease pathogenesis, prompting the suggestion that simple organisms use prionlike mechanisms to switch physiological states and thereby adapt to new environments.
Correcting defects at the genetic level should offer the most potent means of ensuring health and well-being. As defined by authors Kay et al., gene therapy is the introduction of nucleic acids into cells for the purpose of altering the course of a medical condition or disease. In general, with some exceptions, the nucleic acids are DNA molecules encoding gene products or proteins. Thus, the gene essentially can be considered a new pharmaceutical agent for treating many types of diseases. But because cells and organisms have developed powerful mechanisms to avoid the accumulation of extraneous genetic material, routine gene therapy is quite difficult, involving insertion of the appropriate gene into a target non-germ-cell tissue, such that an appropriate amount of gene product (usually a protein) is produced to correct a given malady.6
The three researchers assert that there are two primary candidates for gene transfer: viral and nonviral vectors. According to them, some believe that viruses will be most successful because they have evolved for millions of years to become efficient vesicles for transferring genetic material into cells, whereas others believe that the side effects of viruses and previous exposures will render the host resistant to transduction (gene transfer into the cell) and therefore preclude their long-term use in gene therapy. There are a number of additional viral vectors based on Epstein-Barr virus, herpes, simian virus 40, papilloma, nonhuman lentiviruses, and hepatitis viruses that are currently being evaluated in the laboratory.
Kay et al. remark that once a vector is designed, two general approaches are used for gene transfer: ex vivo, wherein cells are removed, genetically modified, and transplanted back into the same recipient, and in vivo, which is accomplished by transfer of genetic materials directly into the patient. The latter is preferable in most situations, because the complexity of the former method makes it less amenable to wide-scale application.
Frontiers of Science/1997. Mark A. Kay, Dexi Liu, and Peter M. Hoogerbrugge, at <http://www.pnas.org/cgi/content/full/94/24/12744>.