Method and antisense composition for selective inhibition of...

A - Human Necessities – 61 – K

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A61K 47/48 (2006.01) A61K 47/42 (2006.01) A61P 31/18 (2006.01)

Patent

CA 2542875

A method and conjugate for selectively targeting activated hematopoietic cells, e.g., macrophage or T-lymphocyte cells, are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against HIV, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into activated, HIV-infected cells, e.g., activated, HIV-infected macrophage and T-lymphocyte cells. An exemplary embodiment of the invention provides an antisense compound directed to the HIV Vif gene, causing theproduction of defective HIV virions in an infected individual.

L'invention concerne un procédé et un conjugué pour cibler sélectivement des cellules hématopoïétiques activées, par exemple des cellules macrophages ou lymphocytes T. Le conjugué selon l'invention comprend un composé antisens sensiblement non chargé ayant pour cible le VIH, et un polypeptide TAT inverse (rTAT) qui est couplé par covalence avec le composé antisens. Le polypeptide rTAT est efficace pour produire l'absorption sélective du conjugué dans des cellules activées, infectées par le VIH, par exemple dans des cellules macrophages et lymphocytes T activées, infectées par le VIH. Dans un mode de réalisation donné à titre d'exemple, l'invention concerne un composé antisens dirigé contre le gène Vif du VIH qui provoque la production de virions VIH défectueux chez un individu infecté.

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