1987: CRISPR repeats were observed in bacterial genomes. The authors concluded, “no sequence homologous to these has been found elsewhere in procaryotes, and the biological significance of these sequences is not known.” Ishino et al. J. Bacteriology (1987) 169:5429-5433. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC213968/
2002: The term CRISPR was coined to describe the repetitive repeats observed in bacterial and archaeal genomes. Genes usually found associated with the CRISPR repeats were identified and named CRISPR Associated Proteins or Cas. Jansen et al. Mol. Microbiology. (2002) 43:1565-1575. http://www.ncbi.nlm.nih.gov/pubmed/11952905
2005: CRISPR spacer sequences were matched to foreign DNA. Bolotin et al. Microbiology (2005) 151:2551-2561. http://www.ncbi.nlm.nih.gov/pubmed/16079334
2006: CRISPR was first proposed to be a bacterial adaptive immune system. Makarova et al. Biol Direct (2006) 1:7. http://www.ncbi.nlm.nih.gov/pubmed/16545108.
2007: CRISPR loci were found to impart phage resistance in bacteria. It was determined that CRISPR sequences together with the Cas genes impart resistance and that resistance to specific phages was determined by the spacer sequences found between CRISPR repeats. Barrangou et al. Science. (2007) 315:1709-1712. http://www.ncbi.nlm.nih.gov/pubmed/17379808
2009: RNA guided RNA cleavage is first described. Hale et al. RNA (2008) 2:2572-2579. http://www.ncbi.nlm.nih.gov/pubmed/18971321
2010: The CRISPR/Cas system was identified as a bacterial and archeal immune system that targets and cleaves phage DNA. This system was found to be dependent on the bacteria containing CRISPR spacer sequences that match the phage DNA. Additionally researchers discovered that new spacer sequences could be inserted into the bacterial/archeal chromosome making the CRISPR/Cas system an adaptive immune system. Garneau et al. Nature. (2010) 468:67-71. http://www.ncbi.nlm.nih.gov/pubmed/21048762
2011: Cas9 from Streptococcus pyogenes was found to associate with two RNA molecules coined crRNA and tracrRNA and that all these components are required for protection against phage infection. Deltcheva et al. Nature (2011) 471:602-607. http://www.ncbi.nlm.nih.gov/pubmed/21455174
2012: Cas9 was found to be an endonuclease capable of introducing DSB in DNA and that this process is dependent on complementary binding of the crRNA to the target DNA. Two nuclease domains were found in Cas9 with the HNH domain cleaving the complementary strand and the RuvC-like domain cutting the non-complementary strand. Jinek et al. Science (2012) 337:816-821. http://www.ncbi.nlm.nih.gov/pubmed/22745249
2013: The CRISPR/Cas9 system was used to edit targeted genes in both human and mouse cells using designed crRNA sequences. Cong et al. Science (2013) 339:819-823. http://www.ncbi.nlm.nih.gov/pubmed/23287718
First use in plants. Li et al. Nat Biotechnol (2013) 8:688-691. http://www.ncbi.nlm.nih.gov/pubmed/23929339
Also first use in plants ? Nekrasov et al. Nat Biotechnol (2013) 8:691-693. http://www.ncbi.nlm.nih.gov/pubmed/23929340.
2014: The crystal structure of Cas9 complexed with both gRNA and targeted DNA was elucidated. Nishimasu et al. Cell (2014) 156:935-949. http://www.ncbi.nlm.nih.gov/pubmed/24529477
PAMs are identified as a key component of DNA target integration. Anders et al. Nature (2014) 513:569-573. http://www.ncbi.nlm.nih.gov/pubmed/25079318
sgRNA and Cas9 are directly delivered into cells without the use of a vector intermediate. Ramakrishna et al. Genome Res (2014) 24:1020-1027. http://www.ncbi.nlm.nih.gov/pubmed/24696462
2015: CRISPR/Cas9 was used to edit tri-chromosomal pre-implantation human embryos. Researchers attempted to repair the HBB locuswhich, when mutated, results in β-thalassemia blood disorders. The researchers were unable to effectively repair the mutated locus and many off-target cleavages were observed. Liang et al. Protein and Cell (2015) 6:363-372. http://www.ncbi.nlm.nih.gov/pubmed/25894090
2015: An international moratorium is called for making heritable changes to the human genome using gene editing. At an international meeting convened by the National Academy of Science of the United States, the Institute of Medicine, The Chinese Academy of Sciences, and the Royal Society of London scientists called for a moratorium on making inheritable changes to the human genome. None of these groups have regulatory authority to prevent such research from taking place, however previous moratoriums where widely accepted in 1975 when an international group met in California to discuss gene editing in all species.
2016: The USDA determines CRISPR/Cas9 edited crops will not be regulated as GMOs. Due to the lack of foreign DNA and the inability to distinguish CRISPR modified crops from those created by traditional plant breeding the USDA has determined that gene edited crops will not be regulated like traditional GMOs.
2016: The first human trial to use CRISPR gene editing gets approval from the NIH. A National Institute of Health advisory committee approved the use of CRISPR/Cas9 gene editing in a cancer therapy trial. The treatment will use CRISPR/Cas9 technology to edit the patient’s own T cells to target cancer.