Timeline of CRISPR

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This is a timeline of CRISPR (Clustered regularly interspaced short palindromic repeats), a mechanism that allows cells to record over time the viruses that they have been exposed to.

Big picture

Year/period Key developments
1970s The recombinant DNA technology is developed. This would mark the beginning of a new era for biology. For the first time, molecular biologists would gain the ability to manipulate DNA molecules, making it possible to study genes and use them to develop novel medicine and biotechnology.[1]
1980s The polymerase chain reaction revolutionizes molecular biology by making it much easier to quickly copy a piece of DNA thousands of millions of times, speeding the pace of medical research even further.[2]
1987 Yoshizumi Ishino discovers what later would beknown as CRISPR.
2002 CRISPR is characterized and given its name.[3]
2005 CRISPR becomes implicated in immunity.[3]
2007 CRISPR shows to provide acquired resistance against bacterial viruses.[3][4]
2011–present CRISPR starts becoming relevant within the scientific community. Hundreds of millions of dollars would start to be raised as startup capital for biotechnology companies that are using the technique.[5] The number of CRISPR publications would increase by 1,453% from 2011 to 2016.[6] A patent race would start between Berkeley University and the Broad Institute.

Full timeline

Year/period Type of event Event Location
1987 Discovery Japanese molecular biologist Yoshizumi Ishino, working at Osaka University, discovers a new type of repeated sequence in prokaryotes, while studying the escherichia coli gene iap.[7] Japan (Osaka)
1991 Scientific development Researchers discover direct repeats (DRs) in mycobacteria.[3]
1993 Scientific development Spanish microbiologist Francisco Mojica, working at the University of Alicante becomes the first to characterize what is now called a CRISPR locus, a molecular memory of MGE (mobile genetic element) encounters (in other words, a memory of all previous attacks by invaders).[8][9][10] Spain (Alicante)
1993 Scientific development Francisco Mojica and colleagues discover tandem repeats (TREPs) in haloarchaea. The same year, the team reports evidence for TREPs transcription.[3]
1993 Scientific development Researchers develop a method of strain differentiation, direct variable repeat polymer chain reaction (DVR-PCR), which enables typing of individual mycobacterium tuberculosis strains in a single PCR. This would be the first typing method based on the repeats.[3][11]
1995 Scientific development Francisco Mojica and colleagues report evidence of tandem repeats (TREPs) activity while studying Haloferax volcanii and Haloferax mediterranei. [3][12]
1998 Scientific development Researchers find a repeat array in an archaeal conjugative plasmid.[13][3]
2000 (January 18) Scientific development Francisco Mojica and colleagues report recognition and description of what would be described as Short Regularly Spaced Repeats (SRSR) family.[14][3][12][15]
2002 Scientific development Ruud Jansen, working at Utrecht University, introduces the term CRISPR (clustered regularly interspaced short palindromic repeats), to describe the repeats. The same year, Jansen and colleagues report identification of core CRISPR associated genes or cas genes (a number of genes that are always located near the CRISPR sequences and that encode nuclease or helicase proteins, which can cut or unwind DNA).[7][3][16] Netherlands (Utrecht)
2003 Scientific development Researchers report the first experimental identification of a protein interacting with CRISPR DNA repeats.[3]
2005 (May) Scientific development Russian scientist Alexander Bolotin, working at Institut national de la recherche agronomique, discovers an unusual CRISPR locus while studying the bacteria streptococcus thermophilus. Although similar to previously reported systems, the CRISPR array discovered would lack some of the known cas genes and instead contained novel cas genes, including one encoding a large protein they predicted to have nuclease activity, which is now known as Cas9. Bolotin's team would also note that the spacers, which have homology to viral genes, all share a common sequence at one end. This sequence would be later known as protospacer adjacent motif (PAM).[8][3] France
2005 Scientific development Researchers reveal the origin of the spacers in CRISPR elements. This would provide a new and robust identification tool for the CRISPR structure.[17][3]
2005 (November) Scientific development American scientists, working at the The Institute for Genomic Research, classify 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes in prokaryotic genomes.[3][18][15]
2006 Scientific development Russian-American biologist Eugene Koonin and his collaborators, suggest that the CRISPR-Cas system is a prokaryotic RNA interference–based immune system.[7]
2006 Scientific development Researchers report evidence for horizontal transfer of CRISPR systems.[19][7]
2007 Scientific development Researchers classify CRISPR–Cas systems based on repeats.[7]
2007 Scientific development French scientists Rodolphe Barrangou, Philippe Horvath and their collaborators, working at food manufacturing company Danisco, demonstrate that the CRISPR-Cas system provides acquired immunity against bacteriophages.[7][3][4] United States
2008 Scientific development Scientists conceive the term "protospacer" to indicate viral sequence that corresponds to a "spacer" in the CRISPR-Cas9 system.[15]
2008 Scientific development Researchers demonstrate that DNA, not RNA, is the molecular target of most CRISPR-Cas systems.[15]
2008 Scientific development Researchers demonstrate the rapidly changing spacer contents of CRISPR arrays in environmental biofilms.[3]
2008 (August) Scientific development Research teams, working at Wageningen University, University of Sheffield, and the United States National Institutes of Health characterize the RNA processing pathway in CRISPR system.[15]
2008 Scientific development Researchers demonstrate CRISPR interference against plasmids.[3]
2008 Scientific development Researchers identify a ribonucleoprotein complex (Cascade) responsible for processing of pre–crRNA to crRNA (CRISPR RNA).[3]
2008 Scientific development Researchers, working at University of Georgia, and Florida State University, publish the RNA gene silencing pathway involved in the CRISPR-Cas mechanism.
2010 Scientific development The basic function and mechanisms of CRISPR systems become clear, after a variety of research groups begin to harness the natural CRISPR system for various biotechnological applications, including the generation of phage-resistant dairy cultures and phylogenetic classification of bacterial strains.[1]
2010 Scientific development Scientists develop concept of CRISPR autoimmunity.[20][3]
2011 Scientific development Researchers determine through cryo-electron microscopy the structure of type I targeting complex (cascade).[3]
2011 Scientific development Lithuanian biochemist Virginijus Šikšnys and colleagues first demonstrate that the type II CRISPR system is transferrable, in that transplantation of the type II CRISPR locus from streptococcus thermophilus into escherichia coli is able to reconstitute CRISPR interference in a different bacterial strain.[1]
2011 Scientific development Scientists characterize type II Trans-activating crRNA (tracrRNA)–based processing mechanism.[3]
2011 Organization Caribou Biosciences is launched as a CRISPR startup by scientists from the University of California, Berkeley, to drive the commercialization of applications based on the remarkable nucleic acid modification capabilities found in prokaryotic CRISPR systems.[2][21]
2011 Scientific development Team of scientists reclassify Cas proteins and CRISPR systems.[22][3]
2012 Scientific development American biochemist Jennifer Doudna, from UCLA, Berkeley and French professor Emmanuelle Charpentier publish paper A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity, first proposing that CRISPR/Cas9 could be used for programmable gene editing.[15]
2012 Scientific development A few months after Doudna and Charpentier paper, Chinese–American neuroscientist Feng Zhang publishes paper showing how he has successfully harnessed CRISPR with Cas9 to edit a gene in a eukaryotic cell.[2]
2012 (April) Scientific development American conglomerate DuPont starts commercializing the first bacterial cultures based on the CRISPR-Cas 9 technology for the production of pizza cheese.[15] United States
2012 (May) Patent case Jennifer Doudna and Emmanuelle Charpentier submit the first patent application for CRISPR-Cas 9 technology.[15] United States
2012 (August) Engineering Research team, working at the University of California Berkeley publish a new method that harnesses the CRISPR-Cas9 system for genome editing.[15]
2012 Scientific development Researchers report evidence for a positive feedback between active CRISPR spacers and new spacer uptake in a type I–E system.[3]
2012 (December) Patent case The Broad Institute submits fast track application for CRISPR-Cas 9 technology to the United States Patent and Trademark Office. A further dozen patents would be filed by the Institute based on the eukaryotic use of CRISPR.[15][23] United States
2013 (January) Engineering Team led by Feng Zhang at the Broad Institute reports that it has used CRISPR to cut DNA in human cells, opening the door for the tool to be used in medicine.[23][24] In the same month, a number of other researchers at different laboratories publish papers within a few weeks of each other demonstrating how the CRISPR system could be used to edit genomes in human cells.[15]
2013 (January) Engineering CRISPR-Cas systems is used to edit the genome of a zebrafish.[25][15]
2013 (February) Engineering Scientists from Harvard Medical School announce successful RNA-guided editing tool for facile, robust, and multiplexable human genome engineering using a CRISPR-Cas 9 technique.[26][15] United States
2013 (March) Engineering Researchers report the use of type II bacterial CRISPR-Cas system in saccharomyces cerevisiae (a yeast species used in wine making, baking and brewing) for genome engineering.[15][27]
2013 Engineering New CRISPR technology offers the first alternative to the current protein-based targeting (Transcription activator-like effector nuclease and Zinc finger) methods used to specifically target a gene (or other DNA sequence). This new system uses a short RNA to guide a nuclease to the DNA target.[28]
2013 (August) Engineering Scientists demonstrate use of CRISPR/Cas9/sgRNA-mediated targeted gene modification in arabidopsis, tobacco, sorghum and rice.[29]
2013 Engineering A pair of studies simultaneously show how to successfully engineer type II CRISPR systems from streptococcus thermophilus and streptococcus pyogenes to accomplish genome editing in mammalian cells.[1]
2013 (November) Organization Editas Medicine is founded as a transformative genome editing company.[30] United States (Massachusetts)
2013 (November) Organization CRISPR Therapeutics is founded with the mission of developing gene-editing based therapeutics for serious diseases.[31]

[32] || Switzerland

2014 (April 15) Patent case The United States Patent and Trademark Office awards the first patent for use the CRISPR/Cas system to edit eukaryotic genomes to Feng Zhang of the Broad Institute of the MIT.[33] United States
2014 Organization Intellia Therapeutics is launched as a gene editing company, focusing on the development of therapeutics utilizing a the CRISPR/Cas9 system.[34] United States (Cambridge (Massachusets)
2014–2015 Engineering Researchers report the successful use of CRISPR technology in mice to eliminate muscular dystrophy and cure a rare liver disease, and to make human cells immune to HIV.[15]
2015 (March) American scientists call for a voluntary worldwide moratorium on the use of genome editing tools to modify human reproductive cells, under the assumption that genome editing in human embryos using current technologies could have unpredictable effects on future generations.[35]
2015 (April) Engineering Chinese research team reports the first application of CRISPR to (non-viable) human embryos. This development, together with the decreasing costs of the technology would trigger a major bioethical debate about how far CRISPR technology should be used.[15][4] China
2015 (April) Policy The United States National Institutes of Health issues a statement indicating that it will not fund any research that uses genome editing tools such as CRISPR in human embryos.[15]
2015 (September) Leading United Kingdom research organizations issue declare support of the continued use of CRISPR-Cas9 and other genome-editing techniques in preclinical research.[36] United Kingdom
2015 (September) Professor Jennifer Doudna gives a TED Talk about the bioethics of using CRISPR.[37] United Kingdom (London)
2015 (November) Engineering Researchers at University of California campuses in Irvine and San Diego announce they could possibly eliminate malaria using the CRISPR technology to start a gene drive in mosquitos.[38]
2015 (December) Engineering Three different groups of researchers announce they have successfully used CRISPR in mice to treat Duchenne muscular dystrophy (DMD), one rare but among the most common fatal genetic diseases.[38]
2015 (December) Recognition The use of CRISPR/Cas9-gRNA complex for genome editing becomes the American Association for the Advancement of Science choice for breakthrough of the year.[39] United States
2015 (December) Organization German pharmaceutical Bayer announces a joint venture with CRISPR therapeutics with aims at discovering, developing and commercializing potential cures for serious genetic diseases. Bayer would invest US$ 335 million in a long-term alliance through new Bayer LifeScience Center unit.[38][40] Germany
2015 (December) Summit The International Summit on Human Gene Editing is organized at the National Academy of Sciences to discuss gene editing technology, such as altering human eggs, sperm, or early embryos in a way that allows those changes to be inherited by future generations.[15][41] United States
2015 Recognition CRISPR earns recognition as the top scientific breakthrough of the year by Science Magazine.[38] United States
2016 (January) Engineering Scientists at Harvard University publish improved version of CRISPR/Cas 9 with less risk of off-target DNA breaks.[42] United States
2016 (February) Policy The United Kingdom Human Fertilisation and Embryology Authority (HFEA) autorizes researchers get green light to genetically modify human embryos.[43] United Kingdom
2016 (June) Funding American magnate Bill Gates endorses the use of CRISPR technique to create malaria-resistant mosquitoes. By September, the Bill and Melinda Gates Foundation would plan to double the sum it was spending under the Gates–funded project Target malaria, to create a mosquito-killing technology that relies on CRISPR gene editing.[44][45][46]
2017 (February) Patent case The United States Patent and Trademark Office rules that the Broad Institute and University of California, Berkeley ’s patents do not interfere, after lawyers representing the University of California filed for an ‘interference’ proceeding in order to have the Broad’s patents thrown out. The judges' rule, that would benefit Broad Institute, effectively allows both UC-Berkeley and the Broad to have patents covering portions of intellectual property in the CRISPR's field, possibly requiring companies to license patents from both institutions.[47] United States
2017 (April) Engineering A team of scientists from the MIT and Harvard manage to adapt a CRISPR protein that targets RNA (rather than DNA) as a rapid, inexpensive, highly sensitive diagnostic tool.[48] United States
2017 (May) Engineering Research team at Temple University Health System publishes demonstration that HIV-1 replication can be completely shut down and the virus eliminated from infected cells in animals using CRISPR/Cas9 editing technology.[49] United States
2017 (May) Funding The Open Philanthropy Project, a collaboration between Good Ventures and charity evaluator GiveWell, awards a grant of US$ 17,500,000 to Target Malaria over four years to help the project develop and prepare for the potential deployment of gene drive technologies to help eliminate malaria in Sub-Saharan Africa.[50]

See also


  1. 1.0 1.1 1.2 1.3 "Development and Applications of CRISPR-Cas9 for Genome Engineering". doi:10.1016/j.cell.2014.05.010. Retrieved 5 June 2017. 
  2. 2.0 2.1 2.2 "HOW JENNIFER DOUDNA'S GENE EDITING TECHNIQUE WILL CHANGE THE WORLD". bloomberg.com. Retrieved 5 June 2017. 
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 CRISPR-Cas Systems: RNA-mediated Adaptive Immunity in Bacteria and Archaea (Rodolphe Barrangou, John van der Oost ed.). Retrieved 6 June 2017. 
  4. 4.0 4.1 4.2 "A simple guide to CRISPR, one of the biggest science stories of 2016". vox.com. Retrieved 11 June 2017. 
  5. "How CRISPR Gene Editing Works". howstuffworks.com. Retrieved 8 June 2017. 
  6. "Number of CRISPR publications increases by 1,453% from 2011-2016". crisprupdate.com. Retrieved 12 June 2017. 
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Morange, Michel. "CRISPR-Cas: The discovery of an immune system in prokaryotes" (PDF). springer.com. doi:10.1007/s12038-015-9532-6. Retrieved 5 June 2017. 
  8. 8.0 8.1 "CRISPR Timeline". broadinstitute.org. Retrieved 5 June 2017. 
  9. "Comparative Analysis of the Orphan CRISPR2 Locus in 242 Enterococcus faecalis Strains.". US National Library of Medicine. doi:10.1371/journal.pone.0138890. Retrieved 5 June 2017. 
  10. "A Complex of Cas Proteins 5, 6, and 7 Is Required for the Biogenesis and Stability of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-derived RNAs (crRNAs) in Haloferax volcanii". jbc.org. Retrieved 5 June 2017. 
  11. "Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; application for strain differentiation by a novel typing method". wiley.com. Retrieved 6 June 2017. 
  12. 12.0 12.1 "Clustered regularly interspaced short palindromic repeats (CRISPRs): The hallmark of an ingenious antiviral defense mechanism in prokaryotes". researchgate.net. Retrieved 6 June 2017. 
  13. "The CRISPR system: small RNA-guided defense in bacteria and archaea". doi:10.1016/j.molcel.2009.12.033. Retrieved 6 June 2017. 
  14. "Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria". wiley.com. Retrieved 6 June 2017. 
  15. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 "CRISPR". whatisbiotechnology.org. Retrieved 7 June 2017. 
  16. "CRISPR-Cas9". genetherapynet.com. Retrieved 7 June 2017. 
  17. "CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies" (PDF). doi:10.1099/mic.0.27437-0. Retrieved 6 June 2017. 
  18. "A Guild of 45 CRISPR-Associated (Cas) Protein Families and Multiple CRISPR/Cas Subtypes Exist in Prokaryotic Genomes". doi:10.1371/journal.pcbi.0010060. Retrieved 6 June 2017. 
  19. "The repetitive DNA elements called CRISPRs and their associated genes: evidence of horizontal transfer among prokaryotes.". PMID 16612537. doi:10.1007/s00239-005-0223-z. Retrieved 6 June 2017. 
  20. "A model for CRISPR autoimmunity". researchgate.net. Retrieved 6 June 2017. 
  21. "Origins". cariboubio.com. Retrieved 6 June 2017. 
  22. "Mechanism of substrate selection by a highly specific CRISPR endoribonuclease". doi:10.1261/rna.030882.111. Retrieved 7 June 2017. 
  23. "How the battle lines over CRISPR were drawn.". sciencemag.org. Retrieved 7 June 2017. 
  24. "Efficient genome editing in zebrafish using a CRISPR-Cas system". Nature Biotechnology. Retrieved 8 June 2017. 
  25. "RNA-guided human genome engineering via Cas9.". doi:10.1126/science.1232033. Retrieved 8 June 2017. 
  26. "Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems". PMC 3627607Freely accessible. doi:10.1093/nar/gkt135. Retrieved 8 June 2017. 
  27. "CRISPR/Cas9 History". addgene.org. Retrieved 5 June 2017. 
  28. "Demonstration of CRISPR/Cas9/sgRNA-mediated targeted gene modification in Arabidopsis, tobacco, sorghum and rice". oup.com. Retrieved 12 June 2017. 
  29. "Editas Medicine". massbio.org. Retrieved 12 June 2017. 
  30. "CRISPR will Win the Nobel Prize, but When? Not this year…". labiotech.eu. Retrieved 12 June 2017. 
  31. "FOUNDERS & SCIENTIFIC ADVISORS". crisprtx.com. Retrieved 12 June 2017. 
  32. "Patent Covers CRISPR". the-scientist.com. Retrieved 5 June 2017. 
  33. "Company Overview of Intellia Therapeutics Inc.". bloomberg.com. Retrieved 6 June 2017. 
  34. "Don't edit the human germ line". nature.com. Retrieved 12 June 2017. 
  35. "Human genome-editing research should proceed, say leading UK science bodies". wellcome.ac.uk. Retrieved 12 June 2017. 
  36. "How CRISPR lets us edit our DNA". ted.com. Retrieved 5 June 2017. 
  37. 38.0 38.1 38.2 38.3 "CRISPR Is Rapidly Ushering in a New Era in Science". futurism.com. Retrieved 7 June 2017. 
  38. Travis J. "Breakthrough of the Year: CRISPR makes the cut". Science Magazine. American Association for the Advancement of Science. Retrieved 5 June 2017. 
  39. "Bayer and CRISPR Therapeutics AG join Forces to Discover, Develop and Commercialize Potential Cures for Serious Genetic Diseases". bayer.com. Retrieved 7 June 2017. 
  40. "Global summit opens door to controversial gene-editing of human embryos". statnews.com. Retrieved 8 June 2017. 
  41. "High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.". doi:10.1038/nature16526. Retrieved 8 June 2017. 
  42. "British researchers get green light to genetically modify human embryos". theguardian.com. Retrieved 8 June 2017. 
  43. "Bill Gates Doubles His Bet on Wiping Out Mosquitoes with Gene Editing". technologyreview.com. Retrieved 12 June 2017. 
  44. "Bill Gates endorses genetically modified mosquitoes to combat malaria". theverge.com. Retrieved 11 June 2017. 
  45. "Gates Foundation doubling efforts to use CRISPR to create mosquito-killing technology". geneticliteracyproject.org. Retrieved 11 June 2017. 
  46. "Broad Institute wins bitter battle over CRISPR patents". nature.com. Retrieved 7 June 2017. 
  47. "Scientists unveil CRISPR-based diagnostic platform". phys.org. Retrieved 12 June 2017. 
  48. "Gene editing strategy eliminates HIV-1 infection in live animals". sciencedaily.com. Temple University Health System. Retrieved 8 June 2017. 
  49. "Target Malaria — General Support". openphilanthropy.org. Retrieved 12 June 2017.