Patrick Hsu
Salk Institute for Biological Studies
50Publications
15H-index
16.5kCitations
Publications 50
Newest
Published on Nov 5, 2018in Neuro-oncology 9.38
Chidiebere U. Awah (Northwestern University), Edgar Gonzalez-Buendia (Northwestern University)+ 15 AuthorsJan Winter4
Estimated H-index: 4
(German Cancer Research Center)
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Published on Apr 1, 2018in Cell 31.40
Silvana Konermann11
Estimated H-index: 11
(Salk Institute for Biological Studies),
Peter Lotfy2
Estimated H-index: 2
(Salk Institute for Biological Studies)
+ 3 AuthorsPatrick Hsu15
Estimated H-index: 15
(Salk Institute for Biological Studies)
Summary Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity. Here, we analyzed prokaryotic genome and metagenome sequences to identify an uncharacterized family of RNA-guided, RNA-targeting CRISPR systems that we classify as type VI-D. Biochemical characterization and protein engineering of seven distinct orthologs generated a ribonuclease effector derived from Ruminococcus flavefaciens XPD3002 (CasRx) with robust activity in human cells. CasRx-mediated knockd...
34 Citations Source Cite
Published on Dec 1, 2018in Nature Communications 12.35
Josh Tycko3
Estimated H-index: 3
(Stanford University),
Luis A. Barrera15
Estimated H-index: 15
+ 7 AuthorsPatrick Hsu15
Estimated H-index: 15
(Salk Institute for Biological Studies)
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...
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Published on Dec 1, 2018in Nature Communications 12.35
Josh Tycko3
Estimated H-index: 3
(Stanford University),
Luis A. Barrera15
Estimated H-index: 15
+ 7 AuthorsPatrick Hsu15
Estimated H-index: 15
(Salk Institute for Biological Studies)
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 ...
2 Citations Source Cite
Published on Oct 3, 2018in Cell 31.40
Cheng Zhang1
Estimated H-index: 1
(Salk Institute for Biological Studies),
Silvana Konermann11
Estimated H-index: 11
(Salk Institute for Biological Studies)
+ 7 AuthorsDmitry Lyumkis17
Estimated H-index: 17
(Salk Institute for Biological Studies)
Summary CRISPR-Cas endonucleases directed against foreign nucleic acids mediate prokaryotic adaptive immunity and have been tailored for broad genetic engineering applications. Type VI-D CRISPR systems contain the smallest known family of single effector Cas enzymes, and their signature Cas13d ribonuclease employs guide RNAs to cleave matching target RNAs. To understand the molecular basis for Cas13d function and explain its compact molecular architecture, we resolved cryoelectron microscopy str...
3 Citations Source Cite
Published on Aug 1, 2016in Molecular Cell 14.25
Josh Tycko3
Estimated H-index: 3
,
Vic E. Myer19
Estimated H-index: 19
,
Patrick Hsu15
Estimated H-index: 15
(Salk Institute for Biological Studies)
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, ...
77 Citations Source Cite
Published on May 1, 2016in Molecular Therapy 7.01
Josh Tycko3
Estimated H-index: 3
,
Nick Huston + 4 AuthorsDavid Bumcrot12
Estimated H-index: 12
Duchenne muscular dystrophy (DMD) is a recessive X-linked neuromuscular disorder that results in progressive muscle degeneration and premature death. Most patients have exonic deletions in the dystrophin gene that result in a frameshift and nonfunctional protein. In contrast, Becker muscular dystrophy (BMD) patients carry a range of exonic deletions in dystrophin that do not disrupt the reading frame, leading to a much milder disease phenotype. Thus, multiplex CRISPR/Cas9 targeted deletions that...
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Published on Feb 1, 2016in Cell 31.40
Hisato Hirano4
Estimated H-index: 4
(University of Tokyo),
Jonathan S. Gootenberg20
Estimated H-index: 20
+ 9 AuthorsFeng Zhang101
Estimated H-index: 101
Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 A resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-contain...
93 Citations Source Cite
Published on Jun 2, 2016in Nature 41.58
Silvana Konermann11
Estimated H-index: 11
,
Mark D. Brigham12
Estimated H-index: 12
+ 7 AuthorsFeng Zhang101
Estimated H-index: 101
(Broad Institute)
Here the customizable TALE DNA-binding domain was integrated with the light-sensitive cryptochrome 2 protein and its interacting partner (CIB1) from Arabidopsis thaliana, thereby creating an optogenetic two-hybrid system called light-inducible transcriptional effectors (LITEs); the LITE system establishes a novel mode of optogenetic control of endogenous transcription and epigenetic states.
531 Citations Source Cite
Published on Jan 1, 2015in Nature 41.58
Silvana Konermann11
Estimated H-index: 11
,
Mark D. Brigham12
Estimated H-index: 12
+ 9 AuthorsHiroshi Nishimasu23
Estimated H-index: 23
The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.
744 Citations Source Cite
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