Jacob E. Corn
University of California, Berkeley
Genome editingGeneticsBiologyCell biologyCRISPR
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Publications 109
#2Beeke Wienert (UNSW: University of New South Wales)H-Index: 11
Last. Saravanabhavan ThangavelH-Index: 1
view all 15 authors...
Switching hemoglobin synthesis from defective adult beta-globin to fetal gamma-globin is an effective strategy for the treatment of beta-hemoglobinopathies. Fetal hemoglobin expression is down-regulated in the postnatal period due to the interplay of transcription regulators with the HBG promoters. However, in the hereditary persistence of fetal hemoglobin (HPFH) condition, naturally occurring point mutations in the HBG promoter causes continued expression of fetal globin even during adulthood. ...
#1Alan S. Wang (University of California, Berkeley)
#2Leo C. Chen (University of California, Berkeley)
Last. Jonathan Vu (University of California, Berkeley)H-Index: 3
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Summary Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling of transient protein interactions in cell-free Xenopus laevis egg extract identified the dimeric histone chaperone facilitates chromatin transcription (FACT) as an interacto...
#1John C. Rose (Stanford University)H-Index: 5
#2Nicholas A. Popp (UW: University of Washington)H-Index: 1
Last. Douglas M. Fowler (CIFAR: Canadian Institute for Advanced Research)H-Index: 28
view all 9 authors...
CRISPR-Cas9 nucleases are powerful genome engineering tools, but unwanted cleavage at off-target and previously edited sites remains a major concern. Numerous strategies to reduce unwanted cleavage have been devised, but all are imperfect. Here, we report that off-target sites can be shielded from the active Cas9•single guide RNA (sgRNA) complex through the co-administration of dead-RNAs (dRNAs), truncated guide RNAs that direct Cas9 binding but not cleavage. dRNAs can effectively suppress a wid...
1 CitationsSource
#1Beeke Wienert (University of California, Berkeley)H-Index: 11
#2David N. Nguyen (UCSF: University of California, San Francisco)H-Index: 12
Last. Matthew A. M. Carter (Gladstone Institutes)H-Index: 1
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Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other gen...
1 CitationsSource
#1Beeke Wienert (University of California, Berkeley)H-Index: 11
#2Stacia K. Wyman (University of California, Berkeley)H-Index: 5
Last. Jacob E. Corn (ETH Zurich)H-Index: 34
view all 5 authors...
DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR-Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases. Here, we describe a detailed experimental protocol and analysis pipeline with which to perform DISCOVER-seq. The principle of this method is to track the precise recruitment of MRE11 to ...
1 CitationsSource
#1Jin Rui Liang (ETH Zurich)H-Index: 3
#2Emily Lingeman (University of California, Berkeley)H-Index: 4
Last. Jacob E. Corn (ETH Zurich)H-Index: 34
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Summary Selective autophagy of organelles is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few autophagosomal receptors and remodelers. By using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence human ER-phagy factors. Two pathways were unexpectedly required for ER-phagy. First, reduced mitochondrial metabolism represses ER-phagy,...
5 CitationsSource
#1Rutger David Luteijn (University of California, Berkeley)H-Index: 2
#1Rutger D. Luteijn (University of California, Berkeley)H-Index: 8
Last. Joshua J. Woodward (UW: University of Washington)H-Index: 26
view all 11 authors...
#1Mandy Boontanrart (University of California, Berkeley)H-Index: 2
#2Gautier Stehli (ETH Zurich)H-Index: 1
Last. Jacob E. Corn (ETH Zurich)H-Index: 34
view all 10 authors...
Fetal development and anemias such as β-hemoglobinopathies trigger rapid production of red blood cells in a process known as stress erythropoiesis. Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin, which has suggested strategies to treat hemoglobinopathies such as thalassemia and sickle cell disease. However, the mechanisms underlying γ-globin production during cellular stress are still poorly defined. Here we use CRISPR-Cas genome editing and...
1 CitationsSource
#1Charles D. Yeh (ETH Zurich)H-Index: 2
#2Christopher D. Richardson (UCSB: University of California, Santa Barbara)H-Index: 1
Last. Jacob E. Corn (ETH Zurich)H-Index: 34
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Eukaryotic cells deploy overlapping repair pathways to resolve DNA damage. Advancements in genome editing take advantage of these pathways to produce permanent genetic changes. Despite recent improvements, genome editing can produce diverse outcomes that can introduce risks in clinical applications. Although homology-directed repair is attractive for its ability to encode precise edits, it is particularly difficult in human cells. Here we discuss the DNA repair pathways that underlie genome edit...
23 CitationsSource
#1Ron Baik (Stanford University)H-Index: 1
#2Stacia K. Wyman (University of California, Berkeley)H-Index: 5
Last. Jacob E. Corn (ETH Zurich)H-Index: 34
view all 4 authors...
Myeloproliferative neoplasms (MPNs) cause the over-production of blood cells such as erythrocytes (polycythemia vera) or platelets (essential thrombocytosis). JAK2 V617F is the most prevalent somatic mutation in many MPNs, but previous modeling of this mutation in mice relied on transgenic overexpression and resulted in diverse phenotypes that were in some cases attributed to expression level. CRISPR-Cas9 engineering offers new possibilities to model and potentially cure genetically encoded diso...