Targeting of Drugs 5: Strategies for Oligonucleotide and by Charles Coutelle (auth.), Gregory Gregoriadis, Brenda

By Charles Coutelle (auth.), Gregory Gregoriadis, Brenda McCormack (eds.)

Gene remedy for Inherited Genetic disorder; probabilities and difficulties; C. Coutelle. Gene supply and remedy: The Case for Cystic Fibrosis; E.W.F.W. Alton. Immune Responses with Direct Gene move: DNA Vaccines and Implications for Gene remedy; H.L. Davis. Oligonucleotides: Molecular types for optimum Use In Vivo; E.Saison-Behmoaras, et al. Retrovirus Vectors in Gene remedy: focusing on to express Cells; A.J. Kingsman, et al. Adenovirus as Vectors for Gene treatment; M.G. Lee. Receptor-mediated Gene supply with artificial Virus-Like debris; E. Wagner, et al. Controllable Gene Therapy-Recent Advances in Non-Viral Gene supply; A. Rolland. Genetic Chemistry: in the direction of Non-Enzymatic Ligation. Sequence-Selective reputation of DNA and Self-Assembling platforms for Gene supply; J.-P. Behr. Integrin-Mediated Gene supply; S.L. Hart, et al. layout, Synthesis and mobile supply of Antibody specified, Radiolabelled Oligonucleotide Conjugates for melanoma treatment; C.S.R. Gooden, A.A.Epenetos. 7 extra Articles. Index.

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Currently, the most common vaccines are recombinant sub-viral particles containing either only the small S protein produced by yeast cells (Valenzuela et ai, 1982) or the middle or small proteins produced by Chinese hamster ovary cells (Michel et ai, 1984). S respectively) (Davis et ai, 1993b; Michel et ai, 1995). Injection of 50 pg of HBsAg-encoding DNA into the tibialis anterior muscle of the mouse transfects several dozen muscle fibres which are detectable by immunofluorescent labeling as early as 5 days after DNA injection (Davis, Brazolot-Millan and Watkin, unpublished results).

This procedure has the supplementary advantage that the modified linker can function as a universal support, avoiding individual coupling of dC, dT, dG or dA on the solid support (dependent on the selected sequence). As solid support we used Tentage!. This polymeric support, recently introduced in oligonucleotide synthesis, consists of a polystyrene-divinylbenzene copolymer coated with a -70 atom PEG spacer. As this resin swells upon elongation of the oligonucleotide chain, steric hindrance during condensation is minima!.

Transcription can result in production of three different sized polypeptides known as the small (S), middle (preS2 + S) and large (preS I + preS2 + S) proteins. Hepatitis B surface antigen (HBsAg) is the primary antigenic determinant of the HBV envelope protein and is present on all three forms of envelope protein. The envelope of the infectious 42 nm HBV particle (called the Dane particle) contains all three forms, but with a predominance of small proteins and variable amounts of middle and large proteins.

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