1987
|
Short direct repeats were first reported in the genome of the bacterium E. coli.
|
[18] |
2000
|
Repetitive sequence that Ishino found in E. coli also was identified in other bacteria and archaea. |
[19] |
2002
|
-Proposal of CRISPR name and identification of cas gene. |
[109,110] |
-Discovery of transcript of CRISPR. |
2003
|
The first reports of experimental identification of a protein associated with CRISPR DNA repeats. |
[111] |
2005
|
-Discovery of source of spacers from viral origin and plasmid. |
[20] |
-Proposal of idea in which CRISPR-Cas may be an adaptive defense system in bacteria. |
[112] |
-Identification of protospacer-adjacent motif (PAM). |
[113] |
2007
|
First experimental evidence for CRISPR adaptive immune system S. thermophilus.
|
[22] |
2008
|
-Identification of mature CRISPRRNAs (crRNAs) as guides with Cas proteins complex as anti-phage defense system in E. coli. |
[23] |
-Studying the interference activity of Type III (Csm) CRISPR-Cas in Staphylococcus epidermidis. |
[114] |
2009
|
-Investigating the antiviral activity of Pyrococcus furiosus by CRISPR-Cas systems. |
[115] |
-Identification of type III-B Cmr complex that cleaves ssRNA. |
[116] |
2010
|
Identification of cleavage produced by the CRISPR/Cas bacterial immune system at three nucleotides ahead of the PAM sequence. |
[117] |
2011
|
-Classification of three major classes of CRISPR-Cas systems: types I, II, and III. |
[11] |
-Discovery of trans-activating CRISPR RNA (tracrRNA). |
[118] |
-Applying the S. thermophilus type II CRISPR-Cas system in E. coli, reporting that the system is active in some distantly related organisms. |
[119] |
-Discovery of “seed” sequence (the seed sequence or seed region is a conserved heptametrical sequence, which is mostly situated at positions 2–7 from the miRNA 5’-end). |
[120] |
2012
|
-Adaptation of type II CRISPR system (originated from S. pyogenes) for gene editing in mammalian cells. |
[121] |
-First demonstration of programming CRISPR for targeted DNA cleavage in vitro. |
[122] |
2013
|
-Using Cas9 successfully for genome editing in eukaryotic cell. |
[123] |
-Identification of the role of III-B system in transcription-dependent DNA interference. |
[124,125] |
-First use of CRISPR-Cas system in plants. |
[126] |
2014
|
Crystal structure of apo-Cas9, Cas, guide RNA, and target RNA. |
[127,128] |
2015
|
-Crystal structure of chimeric Cmr complex. |
[129] |
-CRISPR/Cas9 was utilized in human embryos. Researchers applied system to repair the HBB locus, which is responsible for β-thalassemia blood disorders when it is mutant. The experiment was not effective due to its off-target activities and impossibility of prediction of gene-editing outcomes through pre-implantation genetic diagnosis (PGD”) |
[130] |
2016
|
-Cmr- and Csm-mediated RNA-activated DNA cleavage discovered |
[24] |
-The first human trial to apply CRISPR gene editing obtained approval from the NIH. |
[131] |
-New approach to genome editing that requires no dsDNA cleavage or a donor template. |
[24,132,133,134] |
2017
|
-Identification of a specific CRISPR protein that targets RNA rather than DNA. |
[32] |
-Developing an efficient version of the CRISPR-Cas9 system called CRISPR-Gold technology that utilizes gold nanoparticles to deliver the CRISPR/Cas9 gene-editing system to cells. |
[135] |
-Identification of base editing. |
[63] |
2018
|
Detected pre-existing antibodies that target Cas9 proteins. Represented the possibility of immune systems responses undermining the use of CRISPR-Cas9 for gene therapy. |
[136] |
2019
|
-Cas12a orthologs showed-editing capacity in human cells. |
[137] |
-BhCas12b was also engineered as a powerful gene-editing tool. |
[138] |
-Many new subtypes of Type-V CRISPR system were identified. |
[139] |
-Cas12k was found as an RNA-guided site-specific integration system in E. coli. |
[140] |
-The Class-I CRISPR system with multiple effectors has been harnessed or using fused FokI domain. |
[141,142] |
2020
|
-CRISPR-Cas12-based detection of SARS-CoV-2. |
[143] |
-Discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPR (Acr) proteins. |
[144] |
2021
|
-‘CRISPRoff’ CRISPR-based tool to switch off genes in human cells without making a single edit to the genetic code is described. |
[145] |
-FDA approves first trial investigating CRISPR gene editing as HIV cure. |
[146] |
-CRISPR is used for molecular genetic control of insect vectors of virus diseases (sterile insect technique). |
[147] |
-CRISPR enzyme’s ancestors reported in microbes |
[148,149] |