Improved antibacterial antisense oligonucleotide and method

Details Improved antibacterial antisense oligonucleotide and method Improved antibacterial antisense oligonucleotide and method

C - Chemistry, Metallurgy

12

N

C12N 15/11 (2006.01) A61K 38/16 (2006.01) A61K 47/48 (2006.01) C07H 21/00 (2006.01) A61K 31/7125 (2006.01) C12N 15/31 (2006.01)

Patent

CA 2660855

A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. Themethod includes one or both of: conjugating an arginine-rich carrier to a 3' or 5' end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.

L'invention concerne un procédé qui permet d'augmenter, d'au moins 10 fois, l'activité antibactérienne d'un oligonucléotide antisens composé de sous-unités morpholino reliées par des liaisons inter-sous-unités contenant du phosphore. Le procédé de l'invention consiste à conjuguer un support riche en arginine à une extrémité 3' ou 5' de l'oligonucléotide et/ou à modifier l'oligonucléotide pour que celui-ci contienne entre 20 % et 50 % de liaisons inter-sous-unités chargées positivement à un pH physiologique. L'invention concerne également un oligonucléotide antisens présentant une activité antibactérienne améliorée par la ou les modifications.

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