Novel nucleic acid/polymer complexes, method for preparing...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/87 (2006.01) A61K 31/70 (2006.01) A61K 47/34 (2006.01) A61K 47/42 (2006.01) A61K 47/48 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2187629

A complex consisting of at least one negatively charged nucleic acid and at least one positively charged polymeric conjugate with an electrostatic bond therebetween, said polymeric conjugate containing a polymer made up of monomeric units supporting free NH¿3??+¿ functions thereof, and being such that the free NH¿3??+¿ functions of said units are substituted in a ratio of at least 10 %, advantageously 45-70 % and particularly 60 %, by uncharged residues causing a reduction in positive charges relative to the unsubstituted polymeric conjugate, whereby release of the nucleic acid by dissociation of the complex is facilitated; said residues also have the properties of comprising at least one hydroxyl group and not corresponding to any recognition signal recognised by a cell membrane receptor; and the free NH¿3??+¿ functions of said units and/or the hydroxyl groups of said residues may also be substituted by at least one molecule forming a recognition signal recognised by a cell membrane receptor, with the proviso that the polymeric conjugate contains at least 30 % of the free NH¿3??+¿ functions.

L'invention concerne un complexe entre au moins un acide nucléique chargé négativement et au moins un conjugué polymérique chargé positivement, la liaison entre l'acide nucléique et le conjugué polymérique étant de nature électrostatique, le conjugué polymérique contenant un polymère formé de motifs monomères portant des fonctions NH3+ libres des susdits motifs et étant tel que: les fonctions NH3+ libres des susdits motifs sont substituées dans un rapport d'au moins 10 %, avantageusement de 45 % à 70 %, notamment de 60 %, par des résidus non chargés entraînant une diminution des charges positives par rapport au même conjugué polymérique non substitué, facilitant le relargage de l'acide nucléique par la dissociation du complexe, les susdits résidus possédant en outre les propriétés suivantes: ils comportent au moins un groupe hydroxyle, ils ne correspondent à aucun signal de reconnaissance reconnu par un récepteur membranaire cellulaire, les fonctions NH3+ libres des susdits motifs et/ou les groupes hydroxyles des susdits résidus pouvant être également substituées par au moins une molécule qui constitue un signal de reconnaissance reconnu par un récepteur membranaire cellulaire, sous réserve que le conjugué polymérique contienne au moins 30 % de fonctions NH3+ libres.

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