Antagonat compositions and methods of use
First Claim
1. A method of upregulating the expression of a single gene in a cell comprising contacting the cell with an antagoNAT, wherein the antagoNAT is a single stranded oligonucleotide comprising 12-27 nucleoside subunits and which:
- is 100% complementary to and specifically hybridizes with a complementary 12-27 nucleotide region of a non-coding natural antisense transcript of the gene; and
comprises at least one sugar modified nucleoside subunit at the 3′
terminus and at least one sugar modified nucleoside subunit at the 5′
terminus; and
further comprises internal sugar modified nucleoside subunits and internal sugar unmodified nucleoside subunits between the 5′
nucleoside subunit and the 3′
nucleoside subunit, and at least one internal nucleoside is modified; and
wherein said antagoNAT upregulates the expression of said gene and wherein the antagoNAT comprises a compound of Formula (I), or a salt thereof;
C-Au-[Bv-A′
w]x-By-A″
2-C
Formula (I)whereineach A, A′
, and A″
independently has the structure of;
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Accused Products
Abstract
Provided herein are compositions, compounds, and methods of modulating gene expression. In certain embodiments described herein is a composition, wherein the composition comprises an antagoNAT. In some embodiments, the antagoNAT is an oligonucleotide comprising modified and unmodified sugar subunits, wherein the antagoNAT hybridizes with a natural antisense transcript. Certain embodiments of the present invention provide a method for modulating gene expression in a cell comprising contacting the cell with an antagoNAT. In some embodiments, the method includes forming a hybrid comprising the antagoNAT and a natural antisense transcript of the gene, wherein the hybrid sterically blocks the normal function of the natural antisense transcript.
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Citations
27 Claims
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1. A method of upregulating the expression of a single gene in a cell comprising contacting the cell with an antagoNAT, wherein the antagoNAT is a single stranded oligonucleotide comprising 12-27 nucleoside subunits and which:
-
is 100% complementary to and specifically hybridizes with a complementary 12-27 nucleotide region of a non-coding natural antisense transcript of the gene; and comprises at least one sugar modified nucleoside subunit at the 3′
terminus and at least one sugar modified nucleoside subunit at the 5′
terminus; andfurther comprises internal sugar modified nucleoside subunits and internal sugar unmodified nucleoside subunits between the 5′
nucleoside subunit and the 3′
nucleoside subunit, and at least one internal nucleoside is modified; andwherein said antagoNAT upregulates the expression of said gene and wherein the antagoNAT comprises a compound of Formula (I), or a salt thereof;
C-Au-[Bv-A′
w]x-By-A″
2-C
Formula (I)wherein each A, A′
, and A″
independently has the structure of; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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Specification