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J. Keith Joung
Harvard University
173Publications
62H-index
25.2kCitations
Publications 173
Newest
#1Killian S. Hanlon (Harvard University)H-Index: 1
#2Benjamin P. Kleinstiver (Harvard University)H-Index: 15
Last.Bence György (Harvard University)H-Index: 20
view all 19 authors...
Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration ...
#1Julian Grünewald (Harvard University)H-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 7 authors...
Cytosine or adenine base editors (CBEs or ABEs) can introduce specific DNA C-to-T or A-to-G alterations1–4. However, we recently demonstrated that they can also induce transcriptome-wide guide-RNA-independent editing of RNA bases5, and created selective curbing of unwanted RNA editing (SECURE)-BE3 variants that have reduced unwanted RNA-editing activity5. Here we describe structure-guided engineering of SECURE-ABE variants with reduced off-target RNA-editing activity and comparable on-target DNA...
#1Kendall R Sanson (Broad Institute)H-Index: 3
#2Peter C DeWeirdt (Broad Institute)
Last.John G. Doench (Broad Institute)H-Index: 29
view all 13 authors...
Cas12a enzymes have attractive properties for scalable delivery of multiplexed perturbations, yet widespread usage has lagged behind Cas9-based strategies. Here we describe the optimization of Cas12a from Acidaminococcus (AsCas12a) for use in pooled genetic screens in human cells. By assaying the activity of thousands of guides, we confirm on-target design rules and extend them to an enhanced activity variant, enAsCas12a. We also develop the first comprehensive set of off-target rules for Cas12a...
#1Bence György (Harvard University)H-Index: 20
#2Carl Nist-Lund (Boston Children's Hospital)H-Index: 3
Last.David P. Corey (Harvard University)H-Index: 75
view all 15 authors...
Since most dominant human mutations are single nucleotide substitutions1,2, we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. However, single nucleotide discrimination can be difficult to achieve3 because commonly used endonucleases, such as Streptococcus pyogenes Cas9 (SpCas9), can tolerate up to seven mismatches between guide RNA (gRNA) and target DNA. Furthermore, the protospacer-adjacent motif (PAM) in some Cas9...
#1Julian Grünewald (Harvard University)H-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 7 authors...
Abstract CRISPR-guided DNA base editors enable the efficient installation of targeted single-nucleotide changes. Cytosine or adenine base editors (CBEs or ABEs), which are fusions of cytidine or adenosine deaminases to CRISPR-Cas nickases, can efficiently induce DNA C-to-T or A-to-G alterations in DNA, respectively1-4. We recently demonstrated that both the widely used CBE BE3 (harboring a rat APOBEC1 cytidine deaminase) and the optimized ABEmax editor can induce tens of thousands of guide RNA-i...
#1Julian GrünewaldH-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith JoungH-Index: 62
view all 7 authors...
CRISPR-Cas base editor technology enables targeted nucleotide alterations and is being rapidly deployed for research and potential therapeutic applications1,2. The most widely used base editors induce DNA cytosine (C) deamination with rat APOBEC1 (rAPOBEC1) enzyme, which is targeted by a linked Cas protein-guide RNA (gRNA) complex3,4. Previous studies of cytosine base editor (CBE) specificity have identified off-target DNA edits in human cells5,6. Here we show that a CBE with rAPOBEC1 can cause ...
#1Kendell Clement (Broad Institute)H-Index: 16
#2Holly A. Rees (Broad Institute)H-Index: 10
Last.Luca Pinello (Broad Institute)H-Index: 22
view all 11 authors...
#1Eric S. LanderH-Index: 252
#2Françoise BaylisH-Index: 24
Last.Ernst-Ludwig WinnackerH-Index: 1
view all 18 authors...
Eric Lander, Francoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework. Eric Lander, Francoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework.
#2Alexander A. Sousa (Harvard University)H-Index: 4
Last.J. Keith JoungH-Index: 62
view all 14 authors...
Broad use of CRISPR–Cas12a (formerly Cpf1) nucleases1 has been hindered by the requirement for an extended TTTV protospacer adjacent motif (PAM)2. To address this limitation, we engineered an enhanced Acidaminococcus sp. Cas12a variant (enAsCas12a) that has a substantially expanded targeting range, enabling targeting of many previously inaccessible PAMs. On average, enAsCas12a exhibits a twofold higher genome editing activity on sites with canonical TTTV PAMs compared to wild-type AsCas12a, and ...
#1Keunsub Lee (Iowa State University)H-Index: 6
#2Yingxiao Zhang (UMD: University of Maryland, College Park)H-Index: 7
Last.Kan Wang (Iowa State University)H-Index: 36
view all 12 authors...
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