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Transcriptional up-regulation of a nearly identical gene,\n                    <jats:italic>SMN2<\/jats:italic>\n                    , can functionally compensate for the loss of\n                    <jats:italic>SMN1<\/jats:italic>\n                    , resulting in increased SMN protein to ameliorate the disease severity. Here we demonstrate that the repressed state of\n                    <jats:italic>SMN2<\/jats:italic>\n                    is reversible by interrupting the recruitment of a repressive epigenetic complex in disease-relevant cell types. Using chemically modified oligonucleotides to bind at a site of interaction on a long noncoding RNA that recruits the repressive complex,\n                    <jats:italic>SMN2<\/jats:italic>\n                    is epigenetically altered to create a transcriptionally permissive state.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1616521114","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T21:00:27Z","timestamp":1487019627000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy"],"prefix":"10.1073","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2766-3256","authenticated-orcid":false,"given":"Caroline J.","family":"Woo","sequence":"first","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena K.","family":"Maier","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Davey","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Brennan","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangde","family":"Li","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"John","family":"Brothers","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Schwartz","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Gordo","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kasper","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor R.","family":"Okamoto","sequence":"additional","affiliation":[{"name":"LGC Biosearch Technologies, Petaluma, CA 94954;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans E.","family":"Johansson","sequence":"additional","affiliation":[{"name":"LGC Biosearch Technologies, Petaluma, CA 94954;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berhan","family":"Mandefro","sequence":"additional","affiliation":[{"name":"Board of Governors\u2013Regenerative Medicine Institute, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Induced Pluripotent Stem Cell Core, The David and Janet Polak Stem Cell Laboratory, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Sareen","sequence":"additional","affiliation":[{"name":"Board of Governors\u2013Regenerative Medicine Institute, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Induced Pluripotent Stem Cell Core, The David and Janet Polak Stem Cell Laboratory, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Department of Biomedical Sciences, Cedars\u2013Sinai Medical Center, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bialek","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Nelson","family":"Chau","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balkrishen","family":"Bhat","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bullough","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Barsoum","sequence":"additional","affiliation":[{"name":"RaNA Therapeutics, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,2,13]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre S","year":"1995","unstructured":"S Lefebvre, , Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155\u2013165 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/hmg\/9.2.259","article-title":"An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN","volume":"9","author":"Lorson CL","year":"2000","unstructured":"CL Lorson, EJ Androphy, An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet 9, 259\u2013265 (2000).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson CL","year":"1999","unstructured":"CL Lorson, E Hahnen, EJ Androphy, B Wirth, A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 96, 6307\u20136311 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani UR","year":"1999","unstructured":"UR Monani, , A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8, 1177\u20131183 (1999).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.neuron.2005.12.001","article-title":"Spinal muscular atrophy: A deficiency in a ubiquitous protein; a motor neuron-specific disease","volume":"48","author":"Monani UR","year":"2005","unstructured":"UR Monani, Spinal muscular atrophy: A deficiency in a ubiquitous protein; a motor neuron-specific disease. 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Nat Genet 16, 265\u2013269 (1997).","journal-title":"Nat Genet"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy","volume":"70","author":"Feldk\u00f6tter M","year":"2002","unstructured":"M Feldk\u00f6tter, V Schwarzer, R Wirth, TF Wienker, B Wirth, Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 70, 358\u2013368 (2002).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","article-title":"Spinal muscular atrophy","volume":"33","author":"Kolb SJ","year":"2015","unstructured":"SJ Kolb, JT Kissel, Spinal muscular atrophy. 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