History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology

Abstract

Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are well-known acquired immunity systems that are widespread in archaea and bacteria. The RNA-guided nucleases from CRISPR-Cas systems are currently regarded as the most reliable tools for genome editing and engineering. The first hint of their existence came in 1987, when an unusual repetitive DNA sequence, which subsequently was defined as a CRISPR, was discovered in the genome during an analysis of genes involved in phosphate metabolism. Similar sequence patterns were then reported in a range of other bacteria as well as in halophilic archaea, suggesting an important role for such evolutionarily conserved clusters of repeated sequences. A critical step toward functional characterization of the CRISPR-Cas systems was the recognition of a link between CRISPRs and the associated Cas proteins, which were initially hypothesized to be involved in DNA repair in hyperthermophilic archaea. Comparative genomics, structural biology, and advanced biochemistry could then work hand in hand, not only culminating in the explosion of genome editing tools based on CRISPR-Cas9 and other class II CRISPR-Cas systems but also providing insights into the origin and evolution of this system from mobile genetic elements denoted casposons. To celebrate the 30th anniversary of the discovery of CRISPR, this minireview briefly discusses the fascinating history of CRISPR-Cas systems, from the original observation of an enigmatic sequence in to genome editing in humans.

A spectacular anomaly in the 4-mer composition of the giant pandoravirus genomes reveals a stringent new evolutionary selection process

“…This suggests that profound and unexpected biological insights may one day come out from the analysis of k-mer frequencies, and in particular from their most improbable fluctuations. In a daring parallel with the delayed understanding of the CRISPR/CAS system from the initial spotting of intriguing repeats 33 , we would like to expect that the pandoraviridae “AGCT” distribution anomaly might lead to the discovery of a novel defense mechanism against viral infection.…”

Antibiyotiklere Alternatif Terapi: CRISPR-Cas antimikrobiyalleri

“…The first CRISPRs were detected by Ishino et al 1987 in iap gene of Escherichia coli genome. Ishino et al discovered an orderly spaced short repeats located in the iap gene but their function had not been exactly figured out (Ishino et al, 1987;Ishino et al, 2018). In the following years, similar repeat sequences were determined in Mycobacterium tuberculosis, Haloferax mediterranei, Methanocaldococcus jannaschii, Thermotoga maritima and other bacteria -archaea (Sorek et al, 2008).…”

Bridged Nucleic Acids Reloaded

“…These researchers concluded that BNA NC -containing probes coupled to fluorescently labeled microspheres are suitable reagents to detect DNMT3A R888 mutations [134]. palindromic repeats" (CRISPR) is specific and, in a surprisingly analogous mode to vertebrate immune systems, it requires previous exposure to the foreign genetic material to create a memory record that can elicit a quick response in future exposure events [138].…”

“…In particular, the class 2, type II system, which depends on the endonuclease Cas9, has been developed as a tool for numerous applications such as the generation of mutants, gene editing, bacterial species identification and typing, antibacterial agents, genome wide screening in mammalian cells, regulation of gene expression (through the use of dCas9, a derivative that lost the cleavage activity), and others [138][139][140][141][142].…”