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Josh Tycko
Stanford University
10Publications
4H-index
311Citations
Publications 11
Newest
#1Theresa Maier (University of Cambridge)H-Index: 1
#2Nicolas J. Wheeler (UW: University of Wisconsin-Madison)H-Index: 1
Last.Jutta Reinhard-Rupp (Merck KGaA)H-Index: 6
view all 13 authors...
Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites’ intermediate snail hosts are a crucial part of the ...
Source
#1Josh Tycko (Stanford University)H-Index: 4
#2Michael Wainberg (Stanford University)H-Index: 6
Last.Michael C. Bassik (Stanford University)H-Index: 31
view all 21 authors...
Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression ne...
4 CitationsSource
#1Josh Tycko (Stanford University)H-Index: 4
#2Michael Wainberg (Stanford University)H-Index: 6
Last.Michael C. Bassik (Stanford University)H-Index: 31
view all 21 authors...
Pooled CRISPR-Cas9 screens have recently emerged as a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we conducted a genome-scale screen for essential CTCF loop anchors in the K562 leukemia cell line. Surprisingly, the primary drivers of signal in this screen were single guide RNAs (sgRNAs) with low specificity scores. After removing these guides, we found that ...
1 CitationsSource
#1Josh Tycko (Stanford University)H-Index: 4
#2Luis A. BarreraH-Index: 17
Last.Patrick Hsu (Salk Institute for Biological Studies)H-Index: 17
view all 10 authors...
The original HTML version of this Article incorrectly listed an affiliation of Josh Tycko as ‘Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA’, instead of the correct ‘Present address: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA’. It also incorrectly listed an affiliation of this author as ‘Present address: Arrakis Therapeutics, 35 Gatehouse Dr., Waltham, MA, 02451, USA’.The original HTML version incorrectly list...
1 CitationsSource
#1Josh Tycko (Stanford University)H-Index: 4
#2Luis A. BarreraH-Index: 17
Last.Patrick Hsu (Salk Institute for Biological Studies)H-Index: 17
view all 10 authors...
Therapeutic genome editing with Staphylococcus aureus Cas9 (SaCas9) requires a rigorous understanding of its potential off-target activity in the human genome. Here we report a high-throughput screening approach to measure SaCas9 genome editing variation in human cells across a large repertoire of 88,692 single guide RNAs (sgRNAs) paired with matched or mismatched target sites in a synthetic cassette. We incorporate randomized barcodes that enable whitelisting of correctly synthesized molecules ...
8 CitationsSource
Engineering complex genetic functions in mammalian cells will require predictive models of gene regulation. Since gene expression is stochastic, leading to cell-to-cell heterogeneity, these models depend on single-cell measurements. Here, we summarize recent microscopy and sequencing-based single-cell measurements of transcription and its chromatin-based regulation. Then, we describe synthetic biology methods for manipulating chromatin, and highlight how they could be coupled to single-cell meas...
3 CitationsSource
#1Maxwell R. MumbachH-Index: 16
#2Ansu SatpathyH-Index: 25
Last.Howard Y. ChangH-Index: 137
view all 27 authors...
High-resolution contact maps of active enhancers and target genes generated by H3K27ac HiChIP in primary human cells provide rational guides to link noncoding disease-associated risk variants to candidate causal genes. Genes are validated by CRISPR activation and interference at connected enhancers and eQTL analysis, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases.
122 CitationsSource
#1Gaelen T. Hess (Stanford University)H-Index: 9
#2Josh Tycko (Stanford University)H-Index: 4
Last.Michael C. Bassik (Stanford University)H-Index: 31
view all 4 authors...
The past several years have seen an explosion in development of applications for the CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment of a range of DNA and chromatin-modifying enzymes. While homology-directed repair (HDR) coupled with Cas9 nuclease cleavage has been used with great success to repair and re-write genomes, recently developed base-editing systems present a useful orthogonal strategy to engineer nucleotide substitutions. Base editing re...
75 CitationsSource
#1Maxwell R. Mumbach (Stanford University)H-Index: 16
#2Ansu Satpathy (Stanford University)H-Index: 25
Last.Howard Y. Chang (Stanford University)H-Index: 137
view all 27 authors...
The challenge of linking intergenic mutations to target genes has limited molecular understanding of human diseases. Here, we show that H3K27ac HiChIP generates high-resolution contact maps of active enhancers and target genes in rare primary human T cell subtypes and coronary artery smooth muscle cells. Differentiation of naive T cells to T helper 17 cells or regulatory T cells creates subtype-specific enhancer-promoter interactions, specifically at regions of shared DNA accessibility. These da...
1 CitationsSource
#1Josh TyckoH-Index: 4
#2Vic E. MyerH-Index: 9
Last.Patrick Hsu (Salk Institute for Biological Studies)H-Index: 17
view all 3 authors...
Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing, ...
109 CitationsSource
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