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Nucleic acid therapeutics

Kalota A, Dondeti VR, Gewirtz AM (2006) Progress in Hie development of nucleic acid therapeutics, p. 173-96... [Pg.188]

Wagner E (2008) The silent (R)evolution of polymeric nucleic acid therapeutics. Pharm Res 25 2920-2923... [Pg.20]

Source Opalinska JB, Gewirtz AM. Nucleic-acid therapeutics basic principles and recent applications, Nature Reviews Drug Discovery 1 503-514 (2002). [Pg.81]

Mecfianism of Action A sulfonamide and folate antagonist that blocks bacterial synthesis of essential nucleic acids. Therapeutic Effect Bactericidal in susceptible microorganisms. [Pg.298]

A supported sulfide source has been demonstrated by Zhang et al.16 to synthesize oligonucleotide phosphorothioates (entry 12). Aminodithiazole-thione attached to a methacrylate-ethyleneglycol copolymer is used to efficiently convert a nucleotide phosphite to a phosphorothioate. The product nucleotide possesses protecting groups suitable for solid-phase oligonucleotide synthesis and thus is a valuable building block for nucleic acid therapeutics. [Pg.353]

Despite the enormous potential of gene therapy, safe and efficient delivery of nucleic acid into cells is still a dominant task in current biotechnological research. The majority of nucleic acid therapeutics are to a higher degree dependent on delivery systems for successful therapeutic intervention than conventional drugs. [Pg.223]

As discussed in Chapter 1 (Section 1.1) certain drugs (including peptides, proteins and nucleic acid therapeutics) are unsuitable for oral delivery and must be given intravenously. Research has recently been directed towards the development of alternatives to the parenteral route, such as the transdermal, nasal and other routes thus far discussed in this book, for the systemic delivery of such drugs. [Pg.298]

One of the best understood pathways to induce innate immune activation is the family of Toll-like receptors (TLRs). TLRs detect highly conserved components of pathogens that are not present in our own cells. The TLRs appear to have evolved as a warning system to detect infections, and in some cases they can be triggered by synthetic nucleic acid therapeutics or accidentally by self molecules.34... [Pg.127]

Adverse drug reactions can be induced by drugs of very diverse nature, including antibiotics, low molecular chemicals, or nucleic acids. Such reactions can be induced directly or indirectly in various ways. Direct effects on the immune system can result in immunosuppression, or in immune stimulation such as with some nucleic acid therapeutics siRNAs or AS ODNs. In contrast, indirect immune effects are caused by immune responses to a chemical or to selfdeterminants altered by a chemical such as with low molecular small molecules. [Pg.130]

By nature, the nucleic acid therapeutics have a high negative charge density and are enzymatically labile hydrophilic biomacromolecules thus, efficient delivery of these therapeutics faces similar challenges as the peptide and protein therapeutics. Irrespective of whether the nucleus (in the case of DNA delivery) or the cytoplasm (e.g., for siRNA delivery) of the cell is the intracellular target site, protection and targeting approaches are required to efficiently deliver the drug. [Pg.283]

Parenteral administration is the primary route of testing delivery for nucleic acid therapeutics irrespective of whether systemic or local effects are desired. However, to some extent, pulmonary and oral routes are also investigated as potential routes for local targeting to treat cystic fibrosis or colonic tissue (171-173). For nonparenteral delivery, the use of pharmaceutical excipients in the formulation is critical. In addition, the production costs of nucleic acid therapeutic-containing drug delivery systems should be minimized. Even for intravenously or subcutaneously injected nucleic acid-based therapeutics, the use of protective carriers is most likely necessary, and advantageous as compared to injection of the naked RNA or DNA. Carriers can be divided into viral or... [Pg.283]

Opalinska JB, Gewirtz AM Nucleic-acid therapeutics Basic principles and recent applications, Nat Rev Drug Disc 2002, 1, 503-514. [Pg.1385]


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