Journal ArticleDOI
Refining strategies to translate genome editing to the clinic
TLDR
The advances made in the gene-editing field in recent years are discussed, and priorities that need to be addressed to expand therapeutic genome editing to further disease entities are specified.Abstract:
In this Review, Cathomen and colleagues present the latest advances, including improvements in nuclease specificity and delivery, that will expedite the clinical translation of genome editing.read more
Citations
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Journal ArticleDOI
Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements
TL;DR: It is shown that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases, and the observed genomic damage in mitotically active cells caused by CRISPR–Cas9 editing may have pathogenic consequences.
Journal ArticleDOI
Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects
TL;DR: Recent advances of the three major genome editing technologies are reviewed and the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies are discussed, focusing on eukaryotic cells and animal models.
Therapeutic genome editing: prospects and challenges
TL;DR: Current progress toward developing programmable nuclease–based therapies as well as future prospects and challenges are discussed.
Journal ArticleDOI
Reprogramming human T cell function and specificity with non-viral genome targeting
Theodore L. Roth,Cristina Puig-Saus,Ruby Yu,Ruby Yu,Eric Shifrut,Eric Shifrut,Julia Carnevale,P. Jonathan Li,P. Jonathan Li,Joseph Hiatt,Justin Saco,Paige Krystofinski,Han Li,Victoria Tobin,Victoria Tobin,David N. Nguyen,David N. Nguyen,Michael R. Lee,Amy L. Putnam,Andrea L. Ferris,Jeff W. Chen,Jean Nicolas Schickel,Laurence Pellerin,David Carmody,Gorka Alkorta-Aranburu,Daniela del Gaudio,Hiroyuki Matsumoto,Montse Morell,Ying Mao,Min Cho,Rolen M. Quadros,Channabasavaiah B. Gurumurthy,Baz Smith,Michael Haugwitz,Stephen H. Hughes,Jonathan S. Weissman,Kathrin Schumann,Kathrin Schumann,Jonathan H. Esensten,Andrew P. May,Alan Ashworth,Gary M. Kupfer,Siri Atma W. Greeley,Rosa Bacchetta,Eric Meffre,Maria Grazia Roncarolo,Neil Romberg,Neil Romberg,Kevan C. Herold,Antoni Ribas,Manuel D. Leonetti,Alexander Marson +51 more
TL;DR: A non-viral strategy to introduce large DNA sequences into T cells enables the correction of a pathogenic mutation that causes autoimmunity, and the replacement of an endogenous T-cell receptor with an engineered receptor that can recognize cancer antigens.
Journal ArticleDOI
Gene therapy clinical trials worldwide to 2017: An update
Samantha L. Ginn,Anais K. Amaya,Ian E. Alexander,Ian E. Alexander,Michael Edelstein,Mohammad R. Abedi +5 more
TL;DR: This review presents the analysis of clinical trials that, to the best of the knowledge, have been or are being performed worldwide, and discusses key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies.
References
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Journal ArticleDOI
A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.
Martin Jinek,Krzysztof Chylinski,Krzysztof Chylinski,Ines Fonfara,Michael H. Hauer,Jennifer A. Doudna,Emmanuelle Charpentier +6 more
TL;DR: This study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
Journal ArticleDOI
Multiplex Genome Engineering Using CRISPR/Cas Systems
Le Cong,Le Cong,F. Ann Ran,F. Ann Ran,David M. Cox,David M. Cox,Shuailiang Lin,Shuailiang Lin,Robert P. J. Barretto,Naomi Habib,Patrick D. Hsu,Patrick D. Hsu,Xuebing Wu,Wenyan Jiang,Luciano A. Marraffini,Feng Zhang +15 more
TL;DR: The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage as discussed by the authors.
Multiplex Genome Engineering Using CRISPR/Cas Systems
Le Cong,F. A. Ran,David Benjamin Turitz Cox,Shuailiang Lin,Robert P. J. Barretto,Naomi Habib,Patrick D. Hsu,Xuebing Wu,Wenyan Jiang,Luciano A. Marraffini,Feng Zhang +10 more
TL;DR: Two different type II CRISPR/Cas systems are engineered and it is demonstrated that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
Journal ArticleDOI
RNA-Guided Human Genome Engineering via Cas9
Prashant Mali,Luhan Yang,Kevin M. Esvelt,John Aach,Marc Güell,James E. DiCarlo,Julie E. Norville,George M. Church,George M. Church +8 more
TL;DR: The type II bacterial CRISPR system is engineer to function with custom guide RNA (gRNA) in human cells to establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Journal ArticleDOI
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Alexis C. Komor,Yongjoo Kim,Yongjoo Kim,Michael S. Packer,Michael S. Packer,John A. Zuris,John A. Zuris,David R. Liu,David R. Liu +8 more
TL;DR: E engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C→T (or G→A) substitution.