Harvard University: Timeline of key events

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Zhang, F, Cong, L, Lodato, Kosuri, S, Church, G, Arlotta, P, 'Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription', Nature Biotechnology, 29 (2011), 149–53. 2011-01-19T00:00:00+0000Benacerraf was an immunologist who, based on experiments with guinea pigs in the 1960s, provided the pathway to understand how T lymphocytes recognise structures on the cell surface of foreign substances that invade the body. He showed that immune responses are controlled by genes that exist in a certain area on a certain chromosome. He was awarded the Nobel Prize for Medicine in 1980 for his discoveries of genes that regulate immune responses and the role some of these genes play in autoimmune disorders. Born in Venezuaela and brought up in Paris, Bernaceraf and his parents were forced to move to United States in 1940 because of their Jewish heritage. 2011-08-02T00:00:00+0000HJ Kim, D Huh, G Hamilton, DE Ingber (2012) 'Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow', Lab on a Chip, 12.2012-01-01T00:00:00+0000K-J Jang, AP Mehr, GA Hamilton, LA McPartlin, S Chung, K-Y Suh, D Ingber (2013) 'Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment', Integrative Biology, 2013-04-25T00:00:00+0000Osborn, M J, Starker, C G, McElroy, A N, 'TALEN-based gene correction for epidermyolysis bullosa', Molecular Therapy, 21/6 (2013), 1151-9.2013-06-01T00:00:00+0000The team who did the research was led by Kenneth Chien. L Zangi, KO Lui, A von Gise, et al, 'Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction', Nature Biotechnology, 31/10 (Oct 2013), 898-907.2013-10-01T00:00:00+0000Y-S Torisawa, CS Spina, T Mammoto et al (June 2014) 'Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro', Nature Methods, 11/6, 663-9. 2014-06-01T00:00:00+0000The aim was to to inactivate 62 endogenous retroviruses in the pig embryos. All pigs have these viruses embedded in their genomes. The presence of such viruses, which can transmit diseases like cancer, is a major hurdle to the transplant of pig organs into humans. The gene editing work was carried out by the geneticist George Church of Harvard Medical School. He and his team presented the results to the US National Academy of Sciences. 2015-10-05T00:00:00+0000The technique involved splitting the Cas9 based gene drive system into two physically separate parts. It was published in J E DiCarlo, A Chavez, S L Dietz, K M Esvelt, G M Church, 'Safeguarding CRISPR-Cas9 gene drives in yeast', Nature Biotechnology, doi:10.1038/nbt.3412.2015-11-16T00:00:00+0000The work laid a pathway for using CRISPR to correct genetic mutatiuons in affected tissues of sick patients. It was published in CE Nelson, CH Hakim, DG Ousterout, PI Thakore et al, 'In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy', Science, DOI: 10.1126/science.aad51432015-12-31T00:00:00+0000Kleinstiver, B P, Pattanayak, V, Prew, M S, Tsai, S Q, Nguyen, N T, Zheng, Z, Joung, K, 'High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects', Nature, doi:10.1038.2016-01-06T00:00:00+0000Based on the analysis of data from hundreds of patients, scientists found markers on tumour cells flagging up very early mutations of the disease. The advantage is these appear on all tumour cells, thereby providing a good target for treatment. N. McGranahan, et al, 'Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade', Science, 351/6280 (2016), 1463-69. 2016-03-25T00:00:00+0000A.C. Komor, Y.B. Kim, M.S. Packer, J.A. Zuris, D.R. Liu, 'Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage', Nature, 533/7603 (2016), 420–24.2016-05-16T00:00:00+0000LD Landegger et al, 'A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear', Nature Biotechnology, 6 Feb 2017, doi:10.1038/nbt.37812017-02-06T00:00:00+0000JU Lind, TA Valentine, AD Pasqualini, S Francesco, H Yan (2016) 'Instrumented cardiac microphysiological devices via multimaterial three-?dimensional printing' Nature Materials, 16/3 303–308 (2016).2017-03-01T00:00:00+0000J. S. Gootenberg, O.O. Abudayyeh, J. W. Lee, et al, 'Nucleic acid detection with CRISPR-Cas13a/C2c2', Science, 13 April 2017, eaam9321, DOI: 10.1126/science.aam9321 2017-04-13T00:00:00+0000A Skardal, SV Murphy, M Devarasetty, et al (2017) 'Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform', Scientific Reports, 7, 8837. 2017-08-18T00:00:00+0000L. Xu, et al, 'Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques', Science, 20 September 2017, Science, 20 Sep 2017, eaan8630, DOI: 0.1126/science.aan86302017-09-20T00:00:00+0000Total of 17 boys treated in clinical trial, of which 15 showed marked improvement. Treatment used a modified form of HIV as the vector for infusing corrective genes to generate glial cells. F. Eichler, C. Duncan etl al, 'Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy', NEJM, DOI: 10.1056/NEJMoa17005542017-10-04T00:00:00+0000BA Hassell, G Goyal, E Lee et al (2017) 'Human Organ Chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro', Cell Reports, 21/2, 508-16.2017-10-10T00:00:00+0000
Date Event People Places Sciences
19 Jan 2011US scientists publish a technique for genetically engineering transcription activator-like effectors customised to recognise specific DNA-binding sites which they show is an effective tool for editing mammalian genomesZhang, Cong, Lodato, Kosuri, Church, ArlottaHarvard University, Massachusetts Institute of Technology Gene editing, TALENs
2 Aug 2011Baruj Benacerraf diedBenacerrafHarvard Medical SchoolImmunology
2012Human gut-on-a-chip publishedHyun Jung Kim, Dongeun Huh, Geraldine Hamilton, IngberHarvard University, Wyss InstituteOrgan-on-a-chip
25 Apr 2013Human-kidney on a chip developed to assess drug transport and toxicityKugng-Jin, Jang, Mehr, Geraldine Hamilton, McPartlin, Seyoon Chung, Kahp-Yang Suh, D IngberHarvard University, Wyss InstituteOrgan-on-a-chip
1 Jun 2013Basic studies conducted with TALENs to see if can correct mutant genes associated with Epidermolysis Bullosa, a rare inherited skin disorderOsborn, Starker, Colby, McElroyUniversity of Minnesota, National Centre for Tumor Diseases Heidelberg, German Cancer Research Centre, Harvard UniversityGene Therapy, Gene editing, TALENs
Oct 2013Modified mRNA shown to help improve heart function in miceLior Zangi, Kathy Lui, von Gise, Qing Ma, Ebina,Ptaszek, Spater, Huansheng Xu, Tabebordbar,Gorbatov, Sena, Nahrendorf, David Briscoe,Ronald Li, Amy Wagers, Rossi, William Pu, Kenneth ChienHarvard University, Massachusetts General Hospital, Children's Hospital Boston, Mount Sinai School of Medicine, Karolinska InstitutemRNA, cardiovascular
Jun 2014Bone-marrow-on-a-chip publishedTorisawa, Spina, Tadanori Mammoto, Akiko Mammoto, Weaver, Tat. Collins, IngberHarvard University, Wyss InstituteOrgan-on-a-chip
5 Oct 2015CRISPR/Cas9 modified 60 genes in pig embryos in first step to create organs suitable for human transplantsChurchHarvard UniversityCRISPR-Cas9, Gene editing, Transgenic animals
16 Nov 2015US scientists published a technique for overwriting changes made by CRISPR/Cas 9DiCarlo, Chavez, Dietz, Esvelt, ChurchHarvard University, Swiss Federal Institute of Technology in Zurich CRISPR-Cas9, Gene editing
31 Dec 2015Gene editiing tool, CRISPR, successfully used to improve muscle function in mouse model of Duchenne muscular dystrophyNelson, Gersbach, Hakim, Ousterout, ThakoreDuke University, University of Missouri, University of North Carolina, Massachusetts Institute of Technology, Harvard UniversityCRISPR-Cas9, Gene editing, Gene therapy
6 Jan 2016US scientists published improved version of CRISPR/Cas 9 with less risk of off-target DNA breaksKleinstiver, Pattanayak, Prew, Tsai, Nguyen, Zheng, JoungHarvard UniversityCRISPR-Cas9, Gene editing
25 Mar 2016Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapyMcGranahan, Furness, Rosenthal, Ramskov, Lyngaa, Saini, Jamal-Hanjani, Wilson, Birkbak, Hiley, Watkins, Shafi, Murugaesu, Mitter, Akarca, Linares, Marafioti, Henry, Van Allen, Miao, Schilling, Schadendorf, Garraway, Makarov, Rizvi,m Snyder, Hellman, MerghUniversity College London, Cancer Research UK, Francis Crick Insitute, Dana-Farber Cancer Institute, Broad Institute, University Duisburg-Essen, Memorial Sloan Kettering Cancer Center, Columbia Univertsity, Weill Cornell Medical College, Harvard Medical SImmunology, Cancer immunotherapy, Oncology, Immune checkpoint inhibitors
16 May 2016US scientists publish new base editing technique offering means to alter genome without needing to cleave double-stranded DNA or for a donor DNA templateKomor, Kim, Packer, Zuris, LiuHarvard UniversityCRISPR-Cas9, Gene editing
6 Feb 2017Gene therapy shown to restore hearing in deaf miceLandegger, Pan, Askew, Wassmer, Gluck, Galvin, Taylor, Forge, Sankovic, Holt, VandenbergheEaton Peabody Laboratories, Harvard Medical School, Medical University of Vienna, UCL, Boston's Children's Hospital, Harvard Stem Cell Institute, University of North Carolina, Grousbeck Gene Therapy CenterGene therapy
1 Mar 2017First organ-on-a-chip produced entirely with 3D printingLind, Busbee, Valentine, Pasqualini, Yuan, Yardid, Sung-Jin Park, Kotkian, Nesmith, Patrick campbell, Vlassak, Jennifer Lewis, Kevin ParkerHarvard University, Wyss InstituteOrgan-on-a-chip
13 Apr 2017CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA moleculeAbudayyeh, Bhattacharyya, Collins, Daringe, Donghia, Dy, Essletzbichler, Freije, Hung, Joung, Koonin, Lee, Livny, Myhrvold, Regev, Sabeti, Gootenberg, Verdine, ZhangBroad Institute, Massachusetts Institute of Technology, Harvard University, Howard Hughes Medical Institute CRISPR-Cas9, Gene editing
18 Aug 2017Three-tissue organ-on-a-chip platform created to assess drug responseSkardal, SeanMurphy, Devarasetty, Mead, Hyun-Wook Kang, Young-Joon Seol, Shrike Zhang, Su-Ryon Shin, Liang Zhao, Aleman, Adam Hall, Shupe, Dokmeci, Sang Jin Lee, John Jackson, James Yoo, Hartung, Khademhosseini, Soker, Bishop, Atala Harvard University, Wyss Institute, Wake Forest School of Medicine, Massachusetts Institute of Technology, Johns Hopkins University, University of Konstanz, Konkuk University, King Abdulaziz UniversityOrgan-on-a-chip
20 Sep 2017Combination of three monoclonal antibodies reported to protect monkeys from HIV Xu, Pegu, Rao, Doria-Rose, Beninga, McKee, Lord, Wei, Deng, Louder, Schmidt, Mankoff, Wu, Asokan, Beil, Lange, Leuschner, Kruip, Sendak, Kwon, Zhou, Chen, Bailer, Wang, Choe, Tartaglia, Barouch, O’Dell, Todd, Burton, Roederer, Connors, Koup, Kwong, YangSanhofi, National Institute of Allergy and Infectious Disease, Harvard University, Massachusetts Institute of Technology, Scripps Research Institute, Monoclonal antibodies, Infectious diseases
4 Oct 2017Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys Eichler, Duncan, WilliamsHarvard University, Bluebird Bio, Boston Children’s Hospital Stem cells, Gene therapy
10 Oct 2017Chip created to mimic orthotopic lung cancer growthHassell, Goyal, Esak Lee, Sontheimer-Phelps, Oren Levy, Christopher S Chen, IngberHarvard University, Wyss Institute, University of FreiburgOrgan-on-a-chip

19 Jan 2011

US scientists publish a technique for genetically engineering transcription activator-like effectors customised to recognise specific DNA-binding sites which they show is an effective tool for editing mammalian genomes

2 Aug 2011

Baruj Benacerraf died

2012

Human gut-on-a-chip published

25 Apr 2013

Human-kidney on a chip developed to assess drug transport and toxicity

1 Jun 2013

Basic studies conducted with TALENs to see if can correct mutant genes associated with Epidermolysis Bullosa, a rare inherited skin disorder

Oct 2013

Modified mRNA shown to help improve heart function in mice

Jun 2014

Bone-marrow-on-a-chip published

5 Oct 2015

CRISPR/Cas9 modified 60 genes in pig embryos in first step to create organs suitable for human transplants

16 Nov 2015

US scientists published a technique for overwriting changes made by CRISPR/Cas 9

31 Dec 2015

Gene editiing tool, CRISPR, successfully used to improve muscle function in mouse model of Duchenne muscular dystrophy

6 Jan 2016

US scientists published improved version of CRISPR/Cas 9 with less risk of off-target DNA breaks

25 Mar 2016

Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapy

16 May 2016

US scientists publish new base editing technique offering means to alter genome without needing to cleave double-stranded DNA or for a donor DNA template

6 Feb 2017

Gene therapy shown to restore hearing in deaf mice

1 Mar 2017

First organ-on-a-chip produced entirely with 3D printing

13 Apr 2017

CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA molecule

18 Aug 2017

Three-tissue organ-on-a-chip platform created to assess drug response

20 Sep 2017

Combination of three monoclonal antibodies reported to protect monkeys from HIV

4 Oct 2017

Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys

10 Oct 2017

Chip created to mimic orthotopic lung cancer growth

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