Branched oligonucleotides
AssigneeUniversity of Massachusetts
InventorsAnastasia Khvorova, Matthew Hassler, Julia Alterman, Bruno Miguel da Cruz Godinho
Life of this patent
Estimating the term…
Abstract
Provided herein are branched oligonucleotides exhibiting efficient and specific tissue distribution, cellular uptake, minimum immune response and off-target effects, without formulation.
Claims20
A method of delivering an siRNA molecule to the central nervous system of a subject, the method comprising intrastriatally, intrathecally, or intracerebroventricularly administering to the subject a di-branched oligonucleotide compound comprising two siRNA molecules covalently bound to one another by way of a linker,
- wherein:
- (a) each siRNA molecule of the di-branched oligonucleotide compound comprises an antisense strand having complementarity to a target gene and a sense strand having complementarity to the antisense strand;
- (b) from 80% to 100% of the nucleotides in each siRNA molecule of the di-branched oligonucleotide compound are chemically modified;
- and
- (c) each antisense strand and each sense strand are, independently, from 15 to 30 nucleotides in length;
- and
- (d) wherein the 5′ end of each antisense strand, independently, comprises a terminal group represented by a formula selected from (X1)-(X8):
A method of delivering an siRNA molecule to the central nervous system of a subject, the method comprising intrastriatally, intrathecally, or intracerebroventricularly administering to the subject a di-branched oligonucleotide compound comprising two siRNA molecules covalently bound to one another by way of a linker,
- wherein:
- (a) each siRNA molecule of the di-branched oligonucleotide compound comprises an antisense strand having complementarity to a target gene and a sense strand having complementarity to the antisense strand;
- (b) from 80% to 100% of the nucleotides in each siRNA molecule of the di-branched oligonucleotide compound are chemically modified;
- and
- (c) each antisense strand and each sense strand are, independently, from 15 to 30 nucleotides in length;
- and
- (d) wherein the 5′ end of each antisense strand comprises a terminal group represented by formula (X3):
A method of delivering an siRNA molecule to the central nervous system of a subject, the method comprising intrastriatally, intrathecally, or intracerebroventricularly administering to the subject a di-branched oligonucleotide compound comprising two siRNA molecules covalently bound to one another by way of a linker,
- wherein:
- (a) each siRNA molecule of the di-branched oligonucleotide compound comprises an antisense strand having complementarity to a target gene and a sense strand having complementarity to the antisense strand;
- (b) from 80% to 100% of the nucleotides in each siRNA molecule of the di-branched oligonucleotide compound are chemically modified;
- and
- (c) each antisense strand and each sense strand are, independently, from 15 to 30 nucleotides in length;
- and
- (d) wherein the 5′ end of each antisense strand comprises an (E)-vinylphosphonate terminal group.
Dependencies are inferred from the claim text.