US 11,788,089 B2
Compositions and methods for modulating MECP2 expression
Arthur M. Krieg, Cambridge, MA (US); Romesh R. Subramanian, Framingham, MA (US); James McSwiggen, Arlington, MA (US); and Jeannie T. Lee, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by The General Hospital Corporation, Boston, MA (US)
Filed on May 18, 2020, as Appl. No. 16/876,271.
Application 16/876,271 is a continuation of application No. 15/787,876, filed on Oct. 19, 2017, granted, now 10,655,128.
Application 15/787,876 is a continuation of application No. 14/401,237, abandoned, previously published as PCT/US2013/041394, filed on May 16, 2013.
Claims priority of provisional application 61/648,051, filed on May 16, 2012.
Prior Publication US 2021/0102203 A1, Apr. 8, 2021
Int. Cl. C07H 21/02 (2006.01); C07H 21/04 (2006.01); C12N 15/113 (2010.01); A61K 47/61 (2017.01); A61K 47/64 (2017.01); A61K 31/7115 (2006.01); A61K 31/712 (2006.01); A61K 31/7125 (2006.01); C07H 21/00 (2006.01); A61K 47/54 (2017.01)
CPC C12N 15/113 (2013.01) [A61K 31/712 (2013.01); A61K 31/7115 (2013.01); A61K 31/7125 (2013.01); A61K 47/555 (2017.08); A61K 47/61 (2017.08); A61K 47/64 (2017.08); A61K 47/6455 (2017.08); C07H 21/00 (2013.01); C07H 21/02 (2013.01); C07H 21/04 (2013.01); C12N 2310/11 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/3231 (2013.01)] 21 Claims
 
1. A method of increasing expression of a MECP2 gene in a cell, the method comprising delivering a single stranded oligonucleotide into the cell, wherein the single stranded oligonucleotide
(a) has a sequence 5′-X-Y-Z, wherein X is any nucleotide, Y is a nucleotide sequence of 6 nucleotides in length that is not a seed sequence of a human microRNA, and Z is a nucleotide sequence of 3-23 nucleotides in length,
(b) is complementary with at least 10 consecutive nucleotides of a PRC2-associated region of a MECP2 gene, wherein the PRC2-associated region is a region of the MECP2 gene that has a sequence that occurs at a higher frequency in a sequencing reaction of products of an RNA-immunoprecipitation assay that employs an anti-body that targets Ezh2 to immunoprecipitate RNA-associated PRC2 complexes from cells comprising the MECP2 gene compared to a control sequencing reaction of products of a control RNA-immunoprecipitation assay that employs a control antibody, and
(c) has at least one nucleotide that is a nucleotide analogue.