Harvard University: Timeline of key events

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N.M. Gaudelli, A. Komor, H. A. Rees, M. S. Packer, A. H. Badran, D. I. Bryson, D. R. Liu, 'Programmable base editing of A-T to G-C in genomic DNA without DNA cleavage', Nature (2017), doi:10.1038/nature24644. 2017-10-25T00:00:00+0000Twenty-two patients were treated in the trial over 42 months in six centres around the world. The treatment consisted of taking immature stem cells from the patient's bone marrow and using a harmless virus to infect the cells with a copy of the normal globin gene. The new genetically altered cells were then reintroduced into the patient's bloodstream after their marrow had been cleared of diseased cells using chemotherapy. Nine out of the twenty-two patients severe beta thalassemia were able to cut down on the number of transfusions they needed by 74%, with three of them no longer needing any transfusions at all. The same was true of the twelve out of thirteen patients with less severe thalassemia. A A Thompson et al, 'Gene therapy in patients with transfusion-dependent beta thalassemia', New England Journal of Medicine, 378 (2018), 1479-93.2018-04-19T00:00:00+0000The advantage of the technique is it enables scientists to disable specific genes and correct harmful mutations by providing cells with fresh DNA strands with to repair the cut. Unlike Crispr-Cas9, which chops target DNA in half, prime editing nicks it and then writes a new section of DNA into the specified region. The new procedure was published in AW Anzalone et al, 'Search-and-replace genome editing without double-strand breaks or donor DNA', Nature (2019), https://doi.org/10.1038/s41586-019-1711-42019-10-21T00:00:00+0000Si, N Bai, H, Rodas, M et al (Aug 2021) 'A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics', Nature Biomedical Engineering, 5/8, 815-29.2021-08-01T00:00:00+0000The drug, Azeliragon, had previously be shown to be safe in trials exploring its use for Alzheimer’s disease and diabetic nephropathy. Studies with the chip, created by Ingber and his team at the Wyss Institute, revealed the small molecule drug blocked inflammation-causing cytokines including IL-6, IL-8, and IP-10 as well as RANTES, a major proinflammatory cytokine produced by virus-infected lung cells. Based on the results Phase 2 clinical trials were planned to investigate the drug further for patients hospitaled with severe COVID-19, and in other pulmonary inflammatory diseases including chronic obstructive pulmonary disease and steroid refractory asthma. 2022-02-23T00:00:00+0000Altman was a Canadian molecular biologist who shared the 1989 Nobel Prize for Chemistry for discovering the catalytic properties of RNA. This emerged out of some work Altman carried out between 1978 and 1983 on a bacterial enzyme called RNAs-P. His research helped transform the basic understanding of nuclear acids, which up to this moment had been understood to only carry genetic information. It also opened up the possibility of using genetic engineering to develop new forms of therapy against viral infections. 2022-04-05T00:00:00+0000H Bai, L Si, A Jiang, A, et al (8 April 2022) 'Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip', Nature Communications, 13/1928.2022-04-08T00:00:00+0000
Date Event People Places Sciences
25 Oct 2017Base editing improvements announced for CRISPR technique, providing means to change individual chemical letters of DNA without need to cleave DNAGaudelli, Komor, Rees, Packer, Badran, Bryson, LiuMassachusetts Institute of Technology, Harvard UniversityCRISPR-Cas9, Gene editing
19 Apr 2018Gene therapy shown to be promising treatment in clinical trials for beta thalassemiaThompson, Walters, Kwiatkowski, Rasko, Ribeil, Hongeng, Magrin, Schiller, Payen, Smeraro, Moshous, LefrerNorth Western University, University of California San Francisco, University of California Los Angeles, University of Sydney, University of Paris, Harvard University, Mahidol University, German Cancer Research CentreGene therapy
21 Oct 2019New DNA editing technique called 'prime editing' publishedAnzalone, Randolph, Davis, Sousa, Koblan, Levy, Chen, Wilson, Newby, Ranguram, LiuMassachusetts Institute of Technology, Harvard UniversityCrispr-Cas9, Gene editing,
Aug 2021Human-airway-on-a-chip used to identify antiviral drugs and prophylactics against SARS-CoV-2 virus Longlong Si, Haiqing Bai, Rodas, Wuji Cao, Crystal Yuri Oh, Amanda Jiang, Moller, Daisy Hoagland, Kohei Oishi, Shu Horiuchi , Skyler Uhl, Blanco-Melo, Randy Albrecht, Wen-Chun Liu, Tristan Jordan, Nilsson-Payant , Golynker, Justin Frere?, James Logue?, RHarvard University, Wyss Institute, Icahn School of Medicine at Mount Sinai, University of Maryland School of Medicine, University of Chieti-Pescara, University of PittsburghOrgan-on-a-chip
23 Feb 2022Human Lung Alveolus Chip demonstrated drug to significantly inhibit production of inflammation-causing cytokines triggered by SARS-CoV-2 and other viral infectionsIngberHarvard University, Wyss Institute, Cantex PharmaceuticalsOrgan-on-a-chip
5 Apr 2022Sidney Altman diedAltmanHarvard University, Laboratory of Molecular Biology, Yale UniversityRNA, genetics
8 Apr 2022Human lung aveolus chip reveals mechanical control of immune responses against viral infectionHaiqing Bai, Longlong Si, Amanda Jiang, Chaitra Belgur, Yunhao Zhai, Plebani, Crystal Yuri Oh, Melissa Rodas, Patil, Nurani, Gilpin, Rani Powers, Girija Goyal, Prantil-Baun, IngberHarvard University, Wyss Institute, University of Chieti-PescaraOrgan-on-a-chip

25 Oct 2017

Base editing improvements announced for CRISPR technique, providing means to change individual chemical letters of DNA without need to cleave DNA

19 Apr 2018

Gene therapy shown to be promising treatment in clinical trials for beta thalassemia

21 Oct 2019

New DNA editing technique called 'prime editing' published

Aug 2021

Human-airway-on-a-chip used to identify antiviral drugs and prophylactics against SARS-CoV-2 virus

23 Feb 2022

Human Lung Alveolus Chip demonstrated drug to significantly inhibit production of inflammation-causing cytokines triggered by SARS-CoV-2 and other viral infections

5 Apr 2022

Sidney Altman died

8 Apr 2022

Human lung aveolus chip reveals mechanical control of immune responses against viral infection

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