Timeline of CRISPR
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.
|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.|
|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.|
|1987||Yoshizumi Ishino discovers what later would beknown as CRISPR.|
|2002||CRISPR is characterized and given its name.|
|2005||CRISPR becomes implicated in immunity.|
|2007||CRISPR shows to provide acquired resistance against bacterial viruses.|
|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. The number of CRISPR publications would increase by 1,453% from 2011 to 2016. A patent race would start between Berkeley University and the Broad Institute.|
|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.||Japan (Osaka)|
|1991||Scientific development||Researchers discover direct repeats (DRs) in mycobacteria.|
|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).||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.|
|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.|
|1995||Scientific development||Francisco Mojica and colleagues report evidence of tandem repeats (TREPs) activity while studying Haloferax volcanii and Haloferax mediterranei. |
|1998||Scientific development||Researchers find a repeat array in an archaeal conjugative plasmid.|
|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.|
|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).||Netherlands (Utrecht)|
|2003||Scientific development||Researchers report the first experimental identification of a protein interacting with CRISPR DNA repeats.|
|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).||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.|
|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.|
|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.|
|2006||Scientific development||Researchers report evidence for horizontal transfer of CRISPR systems.|
|2007||Scientific development||Researchers classify CRISPR–Cas systems based on repeats.|
|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.||United States|
|2008||Scientific development||Scientists conceive the term "protospacer" to indicate viral sequence that corresponds to a "spacer" in the CRISPR-Cas9 system.|
|2008||Scientific development||Researchers demonstrate that DNA, not RNA, is the molecular target of most CRISPR-Cas systems.|
|2008||Scientific development||Researchers demonstrate the rapidly changing spacer contents of CRISPR arrays in environmental biofilms.|
|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.|
|2008||Scientific development||Researchers demonstrate CRISPR interference against plasmids.|
|2008||Scientific development||Researchers identify a ribonucleoprotein complex (Cascade) responsible for processing of pre–crRNA to crRNA (CRISPR RNA).|
|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.|
|2010||Scientific development||Scientists develop concept of CRISPR autoimmunity.|
|2011||Scientific development||Researchers determine through cryo-electron microscopy the structure of type I targeting complex (cascade).|
|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.|
|2011||Scientific development||Scientists characterize type II Trans-activating crRNA (tracrRNA)–based processing mechanism.|
|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.|
|2011||Scientific development||Team of scientists reclassify Cas proteins and CRISPR systems.|
|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.|
|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.|
|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.||United States|
|2012 (May)||Patent case||Jennifer Doudna and Emmanuelle Charpentier submit the first patent application for CRISPR-Cas 9 technology.||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.|
|2012||Scientific development||Researchers report evidence for a positive feedback between active CRISPR spacers and new spacer uptake in a type I–E system.|
|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.||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. 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.|
|2013 (January)||Engineering||CRISPR-Cas systems is used to edit the genome of a zebrafish.|
|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.||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.|
|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.|
|2013 (August)||Engineering||Scientists demonstrate use of CRISPR/Cas9/sgRNA-mediated targeted gene modification in arabidopsis, tobacco, sorghum and rice.|
|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.|
|2013 (November)||Organization||Editas Medicine is founded as a transformative genome editing company.||United States (Massachusetts)|
|2013 (November)||Organization||CRISPR Therapeutics is founded with the mission of developing gene-editing based therapeutics for serious diseases.||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.||United States|
|2014 (August)||Biological engineers at the Massachusets Institute of Technology demonstrate that CRISPR genome-editing technique can disrupt a single parasite gene with a success rate of up to 100% — in a matter of weeks. This approach could enable much more rapid gene analysis and boost drug-development efforts.||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.||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.|
|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.|
|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.||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.|
|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.||United Kingdom|
|2015 (September)||Professor Jennifer Doudna gives a TED Talk about the bioethics of using CRISPR.||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.|
|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.|
|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.||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.||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.||United States|
|2015||Recognition||CRISPR earns recognition as the top scientific breakthrough of the year by Science Magazine.||United States|
|2016 (January)||Engineering||Scientists at Harvard University publish improved version of CRISPR/Cas 9 with less risk of off-target DNA breaks.||United States|
|2016 (February)||Policy||The United Kingdom Human Fertilisation and Embryology Authority (HFEA) autorizes researchers get green light to genetically modify human embryos.||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.|
|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.||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.||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.||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.|
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