Nucleic acids based therapeutics(Cardiff University)

Infectious diseases have always been a terrible scourge for humans. The appearance of these plagues, as they were called without distinction, was generally connected to various conditions: asters, climatic changes or religious reasons. The concept of contagious, and then infectious, diseases came slowly. Variolation, i.e. transmission of 'virulent' matter to induce a natural disease and the immunity against it, was brought from Constantinople to England by Lady Montague, in 1721. This 'variolation' technique was also often performed in veterinary medicine against diseases like sheep-pox or pleuropneumonia. As 'vaccination' is the term generally accepted for 'immunisation', variolation can be the word designating such a technique. The second period of the history of immunisation began, in 1880, with the studies of Pasteur and his collaborators. A great number of bacterial vaccines were developed: dead, live but attenuated or only parts of pathogens. The viruses were produced in animals, then in eggs and at last, in tissue cultures. Second generation vaccines appeared with genetic engineering: recombinant vaccines, vector vaccines, nucleic acids vaccines, and markers vaccines, among others. These novel technologies can permit the development of new ones and improve the quality of the vaccines already existing.

The effects of 5‐fluorodeoxyuridine, 5‐fluorouridine, actinomycin D, and p‐fluorophenylalanine on cell division and oral morphogenesis in both exponentially growing and synchronized Tetrahymena pyriformis GL were investigated. All of the inhibitors tested were capable of preventing and/or greatly delaying cell division in both growth situations. Associated with the block of cell division, there were pronounced effects on oral morphogenesis. Following addition of any one of the inhibitors to an exponetially growing culture, the proportion of cells with developing oral primordia (particularly primordia in the process of membranelle formation) declined sharply, and there appeared, after some time, primordia with oral membranelles in the process of resorption. In synchronized cultures, the effects of the inhibitors on specific developmental stages were followed with more precision. Development continued for about 30 minutes after addition, and then stopped in most of the cells. In cells which were undergoing membranelle formation (developmental stages 3 and 4) at the time when the inhibitor took effect, development was halted and oral primordia were resorbed. On the other hand, cells in which membranelle formation was complete or nearly so (stages 5 and 6) continued to develop and eventually divided. Stabilization occurred at late stage 4 with respect to all of the inhibitors considered in this study, as well as with high and low temperatures, considered earlier.At inhibitor concentrations just below those required to permanently block development in all cells, renewed development in some cells was observed several hours after addition of the agent. The oral structures formed during this period were always normal in both size and internal pattern. In this respect the effects of the chemical inhibitors differ from those of high temperature, which not only interferes in the maintenance of development, but also brings about abnormalities in spatial pattern.The following conclusions may be drawn from these studies: (a) both protein and template RNA synthesis must take place during the process of oral development in order to maintain further development; (b) the pattern and size of the oral structures that are formed is not affected by limitation in the supply of protein and RNA precursors.