Modified cells

Biological agent Any of a range of microorganisms which have an adverse effect on human health, including those genetically modified cell cultures and en-doparasites. 

Recombinant protein is a protein produced by a genetically modified cell or an organism, which expresses a DNA that was subjected to recombination and inserted into its genome. 

A clear priority remains to expand the panel of intestinal efflux transporters that are expressed individually in modified cell lines. These research tools will be instrumental in identifying and validating selective probe transporter substrates and inhibitors. The availability of such probes will allow for a better understanding of the influence of transporters on in vivo pharmacokinetics. A similar set of probes has been instrumental in increasing our understanding of the role that cytochrome P450 plays in human pharmacokinetics and in avoiding issues associated with these enzymes. 

Raso, V., and Basala, M. (1984) A highly cytotoxic human transferrin - Ricin A chain conjugate used to select receptor-modified cells./. Biol. Chem. 259, 1143. 

Genders et al. (Eleetrosynthesis Co Inc.) in conjunction with the Ormiston Mining Company [264-266,282a] have developed a new technology which converts sodium sulfate into two useful products ammonium sulfate (used extensively as a fertilizer) and sodium hydroxide, The scheme of the modified cell is shown in Fig. 34. 

Weiss, M. Analysis of some modified, cell-averaging CFAR processors in multiple-target situations, IEEE Transactions on AES, 18, pp. 102-114. 

Loblolly pine modified by 1,6-diisocyanatohexane (HDI) was found to be resistant to attack by G. trabeum at a WPG of 26 % (Chen, 1992c). At 26 % WPG, 6 % of bonded chemical was lost during a 12-week soil decay test. When moist wood was used for reaction, the HDI reacted mainly to form ureas and biurets. It was stated that the decay resistance of HDI modified wood was probably due to the inability of the modified cell wall to absorb sufficient amounts of water to support decay. Although wood reacted with chloro-sulphonyl isocyanate lost only 1.3 % mass when exposed to G. trabeum in a decay test, it was reported that 50 % of the bonded chemical was lost in this test. 

For the in vitro method, some of the patient s tissues, which have the genetic fault, are removed. Cells are selected from these tissues and normal genes are loaded into the cells with vectors. The modified cells are then returned to the patient to correct the genetic fault. With the in situ method, genes encapsulated by the vectors are injected directly into the tissues to be treated. Figure 4.10 shows the basis for gene therapy. 

Currently, more than 400 human somatic cell gene therapy protocols are being tested. Most of these involve the use of genetically modified cells to treat noninherited diseases. For example, normal copies of the p53 tumor suppressor gene are inserted into lung tumors to halt tumor progression, and genetically modified cells have been used to create new coronary vessels in patients with coronary heart disease. Success has also been achieved in the treatment of hereditary disease (most notably, the recent successful treatment of X-linked severe combined immune deficiency see Clinical Correlate). 

Very many technical and commercial factors are important such as the utility of the product (cost-benefit relationships), ease of scale-up, the productivity of the process etc. Process design, for instance, involves a series of choices, such as the use of isolated enzyme or intact microorganism, use of free or immobilised cell or enzyme, use of mutant or genetically modified cell, or batch or continuous processing etc. Such choices depend on other factors such as the availability and cost of precursors, product purity required, intended scale of operation and existing skills and equipment available within the Organisation. 

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