Open Access
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Silvana Konermann,Mark D. Brigham,Alexandro E. Trevino,Julia Joung,Clea Barcena,Patrick D. Hsu,Naomi Habib,Jonathan S. Gootenberg,Hiroshi Nishimasu,Osamu Nureki,Feng Zhang,Omar O. Abudayyeh +11 more
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The article was published on 2016-05-22 and is currently open access. It has received 1792 citations till now. The article focuses on the topics: CRISPR.read more
Citations
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Unique features of long non-coding RNA biogenesis and function
Jeffrey J. Quinn,Howard Y. Chang +1 more
TL;DR: This Review describes special events in the lifetimes of lncRNAs — before, during and after transcription — and discusses how these events ultimately shape the unique characteristics and functional roles of lNCRNAs.
Journal ArticleDOI
The emerging role of lncRNAs in cancer
TL;DR: The strategies that led to the identification of cancer-related lncRNAs and the methodologies and challenges involving the study of these molecules are discussed, as well as the imminent applications of these findings to the clinic.
Journal ArticleDOI
Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers
Isaac B. Hilton,Anthony D'Ippolito,Christopher M. Vockley,Pratiksha I. Thakore,Gregory E. Crawford,Timothy E. Reddy,Charles A. Gersbach +6 more
TL;DR: A programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused to the catalytic core of the human acetyl transferase p300 is described, leading to robust transcriptional activation of target genes from promoters and both proximal and distal enhancers.
Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA
Hiroshi Nishimasu,Naoshi Dohmae,Ryuichiro Ishitani,Osamu Nureki,Fei Ran,Patrick D. Hsu,Silvana Konermann,Soraya I. Shehata,Feng Zhang +8 more
TL;DR: The crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 Å resolution and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, paving the way for the rational design of new, versatile genome-editing technologies.
Journal ArticleDOI
Highly efficient Cas9-mediated transcriptional programming
Alejandro Chavez,Jonathan Scheiman,Suhani Vora,Benjamin W. Pruitt,Marcelle Tuttle,Eswar Prasad Ramachandran Iyer,Shuailiang Lin,Samira Kiani,Christopher D. Guzman,Daniel J. Wiegand,Dmitry Ter-Ovanesyan,Jonathan L. Braff,Noah Davidsohn,Benjamin E. Housden,Norbert Perrimon,Ron Weiss,John Aach,James J. Collins,George M. Church +18 more
TL;DR: An improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9 is described and demonstrated in activating endogenous coding and noncoding genes and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).
References
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Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Luke A. Gilbert,Max A. Horlbeck,Britt Adamson,Jacqueline E. Villalta,Yuwen Chen,Evan H. Whitehead,Carla P. Guimaraes,Barbara Panning,Michael C. Bassik,Lei S. Qi,Martin Kampmann,Jonathan S. Weissman,Hidde L. Ploegh +12 more
TL;DR: In this article, the authors identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators (CRisPRa) to endogenous genes via endonuclease-deficient Cas9.
Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA
Hiroshi Nishimasu,Naoshi Dohmae,Ryuichiro Ishitani,Osamu Nureki,Fei Ran,Patrick D. Hsu,Silvana Konermann,Soraya I. Shehata,Feng Zhang +8 more
TL;DR: The crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 Å resolution and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, paving the way for the rational design of new, versatile genome-editing technologies.
Journal ArticleDOI
RNA-guided gene activation by CRISPR-Cas9-based transcription factors
Pablo Perez-Pinera,D. Dewran Kocak,Christopher M. Vockley,Andrew F. Adler,Ami M. Kabadi,Lauren R. Polstein,Pratiksha I. Thakore,Katherine A. Glass,David G. Ousterout,Kam W. Leong,Kam W. Leong,Farshid Guilak,Gregory E. Crawford,Timothy E. Reddy,Charles A. Gersbach +14 more
TL;DR: A Cas9-based transactivator that is targeted to DNA sequences by guide RNA molecules is created, demonstrating a simple and versatile approach for RNA-guided gene activation.
Journal ArticleDOI
G-protein-coupled receptors and cancer.
TL;DR: This Review will address the current understanding of the many roles of GPCRs and their signalling circuitry in tumour progression and metastasis and discuss how interfering with GPCR might provide unique opportunities for cancer prevention and treatment.
Journal ArticleDOI
Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K
Jessie Villanueva,Adina Vultur,John T. Lee,Rajasekharan Somasundaram,Mizuho Fukunaga-Kalabis,Angela K. Cipolla,Bradley Wubbenhorst,Xiaowei Xu,Phyllis A. Gimotty,Damien Kee,Ademi Santiago-Walker,Richard Letrero,Kurt D'Andrea,Anitha Pushparajan,James Hayden,Kimberly Dahlman Brown,Sylvie Laquerre,Grant A. McArthur,Jeffrey A. Sosman,Katherine L. Nathanson,Meenhard Herlyn +20 more
TL;DR: Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF- 1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors.