Oligonucleotide analogs having cationic intersubunit linkages

Details Oligonucleotide analogs having cationic intersubunit linkages Oligonucleotide analogs having cationic intersubunit linkages

C - Chemistry, Metallurgy

12

N

C12N 15/11 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2651881

Morpholino oligomers containing both uncharged and cationic intersubunit linkages are provided. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. The presence of the cationic intersubunit linkages in the oligomers, typically at a level of about 10-50% of total linkages, provides enhanced antisense activity, in various antisense applications, relative to the corresponding uncharged oligomers. Also provided are such oligomers conjugated to peptide transporter moieties, where the transporters are preferably composed of arginine subunits, or arginine dimers, alternating with neutral amino acid subunits.

La présente invention concerne des oligomères morpholino contenant à la fois des liaisons cationiques et des liaisons non chargées entre les sous-unités. Les oligomères sont des analogues d'oligonucléotides contenant des séquences prédéterminées de fractions d'appariement des bases. La présence des liaisons cationiques entre les sous-unités dans les oligomères, spécifiquement à un niveau compris entre environ 10 et 50% de toutes les liaisons, assure une activité antisens améliorée, dans diverses applications antisens, par rapport aux oligomères non chargés correspondants. Cette invention concerne également de tels oligomères conjugués à des fractions transporteur de peptide, lesdits transporteurs étant de préférence composés de sous-unités arginine ou de dimères arginine, qui alternent avec des sous-unités d'acide aminé neutre.

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