Antisense antibacterial cell division composition and method

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/11 (2006.01) A23K 1/16 (2006.01) A23K 1/17 (2006.01) A61K 31/712 (2006.01) A61K 31/7125 (2006.01) A61P 31/04 (2006.01) C07H 21/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2396068

Antisense oligomers directed to bacterial cell division and cell cycle- encoding nucleic acids are capable of selectively modulating the biological activity thereof, and are useful in treatment and prevention of bacterial infection. The antisense oligomers are substantially uncharged, and contain from 8 to 40 nucleotide subunits, including a targeting nucleic acid sequence at least 10 nucleotides in length which is effective to hybridize to (i) a bacterial tRNA or (ii) a target sequence, containing a translational start codon, within a bacterial nucleic acid which encodes a protein associated with cell division or the cell cycle. Such proteins include zipA, sulA, secA, dicA, dicB, dicC, dicF, ftsA, ftsI, ftsN, ftsK, ftsL, ftsQ, ftsW, ftsZ, murC, murD, murE, murF, murG, minC, minD, minE, mraY, mraW, mraZ, seqA, ddlB, carbamate kinase, D-ala D-ala ligase, topoisomerase, alkyl hydroperoxide reductase, thioredoxin reductase, dihydrofolate reductase, and cell wall enzyme.

La présente invention concerne des oligomères antisens dirigés contre des acides nucléiques bactériens impliqués dans le codage de la division et du cycle cellulaires, qui sont capables de moduler sélectivement l'activité biologique de ces acides nucléiques et qui sont utilisés dans le traitement et la prévention de l'infection bactérienne. Les oligomères antisens sont sensiblement non chargés, et ils renferment entre 8 et 40 sous-unités nucléotidiques, y compris une séquence d'acide nucléique de ciblage d'au moins 10 nucléotides de long qui est efficace pour s'hybrider avec (i) un ARNt bactérien ou (ii) une séquence cible, contenant un codon initiateur de translation, à l'intérieur d'un acide nucléique bactérien codant une protéine associée à la division ou au cycle cellulaire. Les protéines telles que la protéine précitée comprennent: la zip A, sulA, secA, dicA,dicB, dicC, dicF, ftsA, ftsI, ftsN, ftsK, ftsL, ftsQ, ftsW, ftsZ, murC, murD, murE, murF, murG, minC, minD, minE, mraY, mraW, mraZ, seqA, ddlB, la carbamate kinase, D-ala D-ala ligase, topoisomérase, alkyl hydroperoxyde réductase, thiorédoxine réductase, dihydrofolate réductase, et l'enzyme de la paroi cellulaire.

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