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The synthesis of the tertbutyldimethylsilyl derivatives of adenosine is described. The 2',5'-protected nucleosides were rapidly and easily prepared in relatively good yields. / The silylated nucleosides are easily incorporated into ribonucleotides using the fast and efficient dichlorophosphite method. The ribonucleotide GpCpApApCpCpA corresponding to the 3'-terminus of / (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) / was successfully synthesized in a stepwise fashion. The stepwise and block condensation pathways were compared in the synthesis of CpCpCpCpC. The syntheses of A2'p5'A2'p5'A and other 2',5'- and symmetrically-linked ribonucleotides were readily accomplished. ('31)P NMR was very useful in elucidating the structure of the diribonucleoside monophosphates. A study of the effect of temperature and solvents on yield of final product is undertaken. Various phosphate protecting groups are also evaluated. / A suitable deprotection procedure is investigated and the identity of the phosphate linkages confirmed by enzyme degradations.

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RNA interference (RNAi) is a gene silencing mechanism induced by double-stranded RNA (dsRNA). RNAi has been used extensively to create loss-of-function mutants in many species to identify the functions of genes, but it also has the potential to be used as a species-specific pesticide if the dsRNA can silence essential genes in pests. The mosquito Aedes aegypti is a vector of numerous viruses including Dengue and West Nile virus, and is frequently controlled by chemical insecticides. With growing concerns about the extensive use of broad-spectrum pesticides, new control methods are eagerly sought. In this study, I examined the efficacy of feeding pesticidal dsRNAs to mosquito larvae. A dose-dependent RNAi response and mortality was observed when larvae were fed dsRNA targeting several different genes. Unlike RNAi in the related dipteran Drosophila melanogaster, RNAi in A. aegypti also appeared to be systemic, spreading beyond the gut to other tissues. A degree of species-specificity was also observed, as dsRNA specific to the D. melanogaster β-tubulin gene killed D. melanogaster larvae but did not kill mosquito larvae. RNAi was also used to determine the function of a newly-identified A. aegypti cytochrome P450 (CYP) gene, Aacyp. This gene showed male-biased expression in the mosquitoes, and was expressed primarily in the male abdomen and/or thorax, but unlike some other insect male-biased CYPs, Aacyp was not highly expressed in the reproductive structures. While dsRNA injections successfully knocked down expression of Aacyp, no discernable change in reproductive or male-specific behaviours were noted. Nevertheless, RNAi is still considered a highly versatile tool for both gene function studies and has promising potential to be developed into a novel class of pesticides.