Gene expression with covalently modified polynucleotides
First Claim
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1. A complex for delivering a nucleic acid to a cell, comprising:
- said nucleic acid modified at the N7 positions of guanines in the nucleic acid with a plurality of alkylating agents selected from the list consisting of;
a) compounds having a group containing three or more positively charge groups and a net positive charge linked to a mustard or three-membered ring nucleic acid reactive group;
b) compounds having three mustard nucleic acid reactive groups; and
wherein reaction with the nucleic acid crosslinks the nucleic acid; and
,c) compounds having a sulfhydryl or disulfide group and a mustard or three-membered ring nucleic acid reactive group wherein the sulfhydryl or disulfide groups are oxidized or exchanged to form disulfide bonds between pairs of compounds attached to the nucleic acid, thereby crosslinking the nucleic acid;
wherein said modification compacts, reduces the volume of, or reduces the hydrodynamic radius of the nucleic acid when compared to the unmodified nucleic acid.
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Abstract
A process and compound wherein nucleic acids can be modified with a host of molecules and maintain their ability to be expressed. A modifying chemical attachment of polyions to polynucleotides can be used to facilitate the change of tertiary structure of the nucleic acid and in some cases condensation of nucleic acids into smaller, charged particles useful in delivering the nucleic acid to a cell.
5 Citations
14 Claims
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1. A complex for delivering a nucleic acid to a cell, comprising:
- said nucleic acid modified at the N7 positions of guanines in the nucleic acid with a plurality of alkylating agents selected from the list consisting of;
a) compounds having a group containing three or more positively charge groups and a net positive charge linked to a mustard or three-membered ring nucleic acid reactive group; b) compounds having three mustard nucleic acid reactive groups; and
wherein reaction with the nucleic acid crosslinks the nucleic acid; and
,c) compounds having a sulfhydryl or disulfide group and a mustard or three-membered ring nucleic acid reactive group wherein the sulfhydryl or disulfide groups are oxidized or exchanged to form disulfide bonds between pairs of compounds attached to the nucleic acid, thereby crosslinking the nucleic acid; wherein said modification compacts, reduces the volume of, or reduces the hydrodynamic radius of the nucleic acid when compared to the unmodified nucleic acid. - View Dependent Claims (2, 3, 4, 5, 6, 7, 11, 12, 13, 14)
- said nucleic acid modified at the N7 positions of guanines in the nucleic acid with a plurality of alkylating agents selected from the list consisting of;
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8. A complex for delivering a nucleic acid to a cell, comprising:
- said nucleic acid modified at the N7 positions of guanines in the nucleic acid via formation of Lewis acid;
Lewis base complexes with a plurality of modifying agents selected from the group consisting of;a) compounds having a group containing three or more positively charge groups and a net positive charge linked to a Lewis acid, wherein the Lewis acid is not a hydrogen; and
,b) compounds having a sulfhydryl or disulfide group linked to a Lewis acid, wherein the Lewis acid is not a hydrogen, and wherein the sulfydryl or disulfide groups are oxidized or exchanged to form a disulfide bond between pairs of compounds attached to the nucleic acid, thereby crossliniking the nucleic acid; wherein said modification compacts, reduces the volume of, or reduces the hydrodynamic radius of the nucleic acid when compared to the unmodified nucleic acid. - View Dependent Claims (9, 10)
- said nucleic acid modified at the N7 positions of guanines in the nucleic acid via formation of Lewis acid;
Specification