Journal ArticleDOI
Safe harbours for the integration of new DNA in the human genome
TLDR
'genomic safe harbours' are discussed — chromosomal locations where therapeutic transgenes can integrate and function in a predictable manner without perturbing endogenous gene activity and promoting cancer.Abstract:
Interactions between newly integrated DNA and the host genome limit the reliability and safety of transgene integration for therapeutic cell engineering and other applications. Although targeted gene delivery has made considerable progress, the question of where to insert foreign sequences in the human genome to maximize safety and efficacy has received little attention. In this Opinion article, we discuss 'genomic safe harbours' - chromosomal locations where therapeutic transgenes can integrate and function in a predictable manner without perturbing endogenous gene activity and promoting cancer.read more
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The Basic Principles of Chimeric Antigen Receptor Design
TL;DR: This review focuses on the design ofCARs, including the requirements for optimal antigen recognition and different modalities to provide costimulatory support to targeted T cells, which include the use of second- and third generation CARs, costimulation ligands, chimericcostimulatory receptors, and cytokines.
Journal ArticleDOI
A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers
Ashton C. Berger,Anil Korkut,Rupa S. Kanchi,Apurva M. Hegde,Walter F. Lenoir,Wenbin Liu,Yuexin Liu,Huihui Fan,Hui Shen,Visweswaran Ravikumar,Arvind Rao,Andre Schultz,Xubin Li,Pavel Sumazin,Cecilia Williams,Pieter Mestdagh,Preethi H. Gunaratne,Christina Yau,Reanne Bowlby,A. Gordon Robertson,Daniel Guimarães Tiezzi,Chen Wang,Andrew D. Cherniack,Andrew K. Godwin,Nicole M. Kuderer,Janet S. Rader,Rosemary E. Zuna,Anil K. Sood,Alexander J. Lazar,Akinyemi I. Ojesina,Clement Adebamowo,Sally N. Adebamowo,Keith A. Baggerly,Ting-Wen Chen,Hua-Sheng Chiu,Steve Lefever,Liang Liu,Karen L. MacKenzie,Sandra Orsulic,Jason Roszik,Carl Simon Shelley,Qianqian Song,Christopher P. Vellano,Nicolas Wentzensen,John N. Weinstein,Gordon B. Mills,Douglas A. Levine,Rehan Akbani +47 more
TL;DR: Using 16 key molecular features, five prognostic subtypes were identified and a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories was developed, raising potential implications for immunotherapy.
Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT)
TL;DR: The third edition of the TIF guidelines was published by Musallam et al. as mentioned in this paper and includes updated information on new approaches for more effective, safe and less laborious treatment, and an overview of the progress achieved to date towards a total cure using methods such as gene therapy and stem cell transplantation.
Journal ArticleDOI
RNA-guided DNA insertion with CRISPR-associated transposases.
Jonathan Strecker,Alim Ladha,Zachary Gardner,Jonathan L. Schmid-Burgk,Kira S. Makarova,Eugene V. Koonin,Feng Zhang +6 more
TL;DR: This work expands the understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.
Journal ArticleDOI
Delivery technologies for genome editing
TL;DR: The principles of biomacromolecule delivery and gene editing are discussed, recent advances and challenges in non-viral and viral delivery methods are examined, and the status of related clinical trials are highlighted.
References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Integrated genomic analyses of ovarian carcinoma
Debra A. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,M. Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Beth Y. Karlan,Douglas A. Levine,Douglas A. Levine,Douglas A. Levine,Gordon B. Mills,Gordon B. Mills,Carl Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,J. A. Drummond,G. Fowler,Preethi H. Gunaratne,A. C. Hawes,C. L. Kovar,L. R. Lewis,M. B. Morgan,I. F. Newsham,J. Santibanez,Jeffrey G. Reid,L. R. Trevino,Yue Wu,M. Wang,Donna M. Muzny,D. A. Wheeler,Richard A. Gibbs,Gad Getz,Gad Getz,Michael S. Lawrence,Michael S. Lawrence,Kristian Cibulskis,Kristian Cibulskis,Andrey Sivachenko,C. Sougnez,Douglas Voet,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,Kristin G. Ardlie,T. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,M. O'Laughlin,D. J. Dooling,Linnea Fulton,R. Abbott,N. D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Hayden R. Schmidt,Joelle Kalicki,K. D. Delehaunty,Catrina Fronick,Ryan Demeter,L. Cook,J. W. Wallis,L. Lin,Vincent Magrini,J. S. Hodges,James M. Eldred,S. M. Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,R. G.W. Verhaak,Suzie Carter,Craig H. Mermel,G. Saksena,G. Saksena,H. Nguyen,R. C. Onofrio,D. Hubbard,S. Gupta,A. Crenshaw,A. H. Ramos,Lynda Chin,Lynda Chin,Alexei Protopopov,Jinghui Zhang,Jinghui Zhang,Jinghui Zhang,T. M. Kim,Ilana Perna,Y. Xiao,Hailei Zhang,Gang Ren,N. Sathiamoorthy,R. W. Park,R. W. Park,Eunjung Lee,Peter J. Park,Peter J. Park,Raju Kucherlapati,D. M. Absher,L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,L. Cope,James G. Herman,H. Shen,Daniel J. Weisenberger,Houtan Noushmehr,F. Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,J. Buckley,Stephen B. Baylin,Paul T. Spellman,Paul T. Spellman,Elizabeth Purdom,Pierre Neuvial,Pierre Neuvial,Henrik Bengtsson,Henrik Bengtsson,L. R. Jakkula,S. Durinck,S. Durinck,Junhong Han,Junhong Han,S. Dorton,H. Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,J. G. Conboy,Bahram Parvin,H. S. Feiler,Terence P. Speed,Joe W. Gray,Joe W. Gray,N. D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Nikolaus Schultz,L. Borsu,Alex E. Lash,Cameron Brennan,A. Viale,Chris Sander,M. Ladanyi,M. Ladanyi,Katherine A. Hoadley,Katherine A. Hoadley,S. Meng,Y. Du,Y. Du,Yigong Shi,Lulin Li,Y. J. Turman,D. Zang,E. B. Helms,S. Balu,Xiang Zhou,Jane Y. Wu,M. D. Topal,D. N. Hayes,D. N. Hayes,Charles M. Perou,Chaowei Wu,S. Shukla,A. Sivachenko,R. Jing,Yingkai Liu,M. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,A. Olshen,B. Reva,Yevgeniy Antipin,R. Shen,P. Mankoo,Robert L. Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Z. Sanborn,Charles J. Vaske,Jieqing Zhu,Christopher Szeto,G. K. Scott,Christina Yau,Matthew D. Wilkerson,N. Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,T. Shelton,Dirk Grimm,Martha Hatfield,Scott Morris,P. Yena,P. Rhodes,Mark E. Sherman,J. Paulauskis,S. Millis,A. Kahn,John M. Greene,R. Sfeir,M. A. Jensen,John W. Chen,J. Whitmore,S. Alonso,J. Jordan,A. Chu,A. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jane Peterson,Elizabeth J. Thomson +285 more
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Integrated genomic analyses of ovarian carcinoma
Daphne W. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,Mei Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Douglas A. Levine,Gordon B. Mills,Carolyn A. Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Preethi H. Gunaratne,Alicia Hawes,Christie Kovar,Lora Lewis,Margaret B. Morgan,Irene Newsham,Jireh Santibanez,Jeffrey G. Reid,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Donna Muzny,D Wheeler,Richard A. Gibbs,Gad Getz,Michael S. Lawrence,Kristian Cibulskis,Andrey Sivachenko,Carrie Sougnez,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,T. J. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,Michelle D O'Laughlin,David J. Dooling,Linnea Fulton,Rachel Abbott,Nathan D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Heather K. Schmidt,Joelle Kalicki,Kimberly D. Delehaunty,Catrina Fronick,Ryan Demeter,Linda S. Cook,John W. Wallis,Ling Lin,Vincent Magrini,Jennifer S. Hodges,James M. Eldred,Shaleigh Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,Roeland Verhaak,Suzie Carter,Craig H. Mermel,Gordon Saksena,Huy V. Nguyen,Robert C. Onofrio,Diana D. Hubbard,Sonal Gupta,Andrew Crenshaw,Alex H. Ramos,Lynda Chin,Alexei Protopopov,Juinhua Zhang,T. M. Kim,Ilana Perna,Yonghong Xiao,Hailei Zhang,Gang Ren,Narayanan Sathiamoorthy,Richard W. Park,Eunjung Lee,Peter J. Park,Raju Kucherlapati,Devin Absher,Lindsay L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,Leslie Cope,James G. Herman,Hui Shen,Daniel J. Weisenberger,Houtan Noushmehr,Fei Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,Jonathan D. Buckley,Stephen B. Baylin,P. Spellman,Elizabeth Purdom,Pierre Neuvial,Henrik Bengtsson,Lakshmi Jakkula,Steffen Durinck,Junhong Han,Shannon Dorton,Henry Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Joe W. Gray,Nicholas D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Laetitia Borsu,Alex E. Lash,Cameron Brennan,Agnes Viale,Chris Sander,M. Ladanyi,Katherine A. Hoadley,Shaowu Meng,Ying Du,Yan Shi,Lulin Li,Yidi J. Turman,D. Zang,E. B. Helms,Saianand Balu,Xiang Zhou,Jane Y. Wu,Michael D. Topal,David N. Hayes,Charles M. Perou,Junihua Zhang,Chaowei Wu,Sachet A. Shukla,Andrey Sivachenko,Rui Jing,Yingkai Liu,Michael S. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,Adam B. Olshen,Boris Reva,Yevgeniy Antipin,Ronglai Shen,Parminder K. Mankoo,Rachael Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,John Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Matthew D. Wilkerson,Nianxiang Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,Troy Shelton,Dirk Grimm,Martha Hatfield,Shannon R. Morris,Peggy Yena,P. Rhodes,Mark E. Sherman,Joseph Paulauskis,S. Millis,Ari B. Kahn,John M. Greene,Robert Sfeir,Mark A. Jensen,John W. Chen,Jon Whitmore,Shelley Alonso,Justin T. Jordan,Anna L. Chu,Jinghui Zhang,Anna D. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jessica L. Peterson,E. Thomson +261 more
TL;DR: The Cancer Genome Atlas project has analyzed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours as mentioned in this paper.
Journal ArticleDOI
LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.
Salima Hacein-Bey-Abina,C von Kalle,C von Kalle,Manfred Schmidt,Matthew P. McCormack,NM Wulffraat,Philippe Leboulch,Annick Lim,Cameron S. Osborne,R. Pawliuk,Estelle Morillon,R. Sorensen,A. Forster,Peter Fraser,Jeffrey I. Cohen,G de Saint Basile,Ian E. Alexander,Uwe Wintergerst,Thierry Frebourg,Alain Aurias,Dominique Stoppa-Lyonnet,Serge Romana,I. Radford-Weiss,Fabian Gross,Françoise Valensi,Eric Delabesse,Elizabeth Macintyre,F. Sigaux,Jean Soulier,L. E. Leiva,Manuela Wissler,Claudia Prinz,Terence H. Rabbitts,F. Le Deist,Alain Fischer,Marina Cavazzana-Calvo +35 more
TL;DR: Retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
PatentDOI
Consensus coding sequences of human breast and colorectal cancers
Tobias Sjöblom,Sian Jones,D. Williams Parsons,Laura D. Wood,Jimmy Lin,Thomas D. Barber,Diana Mandelker,Bert Vogelstein,Kenneth W. Kinzler,Victor E. Velculesu +9 more
TL;DR: In this paper, the authors analyzed 13,023 genes in 11 breast and 11 colorectal cancers and found that individual tumors accumulate an average of 90 mutant genes but only a subset of these contribute to the neoplastic process.
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