Conjugates and methods of forming conjugates of oligonucleotides and carbohydrates

A complex comprising a conjugate having an oligonucleotide and a carbohydrate coupled thereto by a crosslinker interposed between said oligonucleotide and said carbohydrate, said crosslinker being 1,5-bis(succinimidooxycarbonyloxy) pentane, wherein said conjugate is bound to a macromolecule selected from the group consisting of mRNA and double-stranded DNA.

A method of forming a conjugate having an oligonucleotide and a carbohydrate coupled thereto, including the steps of:

• providing an oligonucleotide, a carbohydrate and a crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000;
• and reacting said oligonucleotide with said carbohydrate and crosslinker to form said conjugate, said reacting step being catalyzed by an enzyme.

A conjugate having an oligonucleotide and a carbohydrate coupled thereto by a crosslinker interposed between said oligonucleotide and said carbohydrate, said crosslinker being 1,5-bis(succinimidooxycarbonyloxy) pentane.

A complex comprising a conjugate having an oligonucleotide and sucrose coupled thereto by a crosslinker interposed between said oligonucleotide and said sucrose, said crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000 wherein said conjugate is bound to a macromolecule selected from the group consisting of mRNA and double-stranded DNA.

A method of forming a conjugate having an oligonucleotide and sucrose coupled thereto, including the steps of:

• providing an oligonucleotide, sucrose, and a crosslinker comprising a non-naturally occurring, non-proteinaceous electrically neutral synthetic compound having a molecular weight of up to about 20,000;
• and
• reacting said oligonucleotide with said sucrose and crosslinker to form said conjugate.

A method of forming a conjugate having an oligonucleotide and a carbohydrate coupled thereto, including the steps of:

• providing an oligonucleotide a carbohydrate and a crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000;
• and
• reacting said oligonucleotide with said carbohydrate and crosslinker to form said conjugate, said crosslinker being 1,5-bis(succinimidooxycarbonyloxy) pentane.

A conjugate having an oligonucleotide presenting opposed terminal 3′ and 5′ ends and a sugar comprising sucrose coupled thereto by a crosslinker interposed between said oligonucleotide and said sugar, neither said sugar, oligonucleotide, nor crosslinker containing an amino acid residue moiety exceeding 10 amino acid residues in length, said crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000, and said crosslinker being covalently coupled to one of said oligonucleotide ends.

A complex comprising a conjugate having an oligonucleotide presenting opposed 3′ and 5′ terminal ends, and a sugar comprising sucrose coupled thereto by a crosslinker interposed between said oligonucleotide and said sugar, neither said sugar, oligonucleotide, nor crosslinker containing an amino acid residue moiety exceeding 10 amino acid residues in length, said crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000, wherein said conjugate is bound to a macromolecule selected from the group consisting of mRNA and double-stranded DNA, said crosslinker being covalently coupled to one of said oligonucleotide ends.

A method of forming a conjugate having an oligonucleotide and a sugar coupled thereto, including the steps of:

• providing an oligonucleotide presenting opposed 3′ and 5′ terminal ends, a sugar comprising sucrose and a crosslinker comprising a non-naturally occurring, non-proteinaceous, electrically neutral synthetic compound having a molecular weight of up to about 20,000;
• and
• reacting said oligonucleotide with said sugar and crosslinker to form said conjugate, said crosslinker being covalently coupled to one of said oligonucleotide ends, neither said sugar, oligonucleotide, nor crosslinker containing an amino acid residue moiety exceeding 10 amino acid residues in length.