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Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems.

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TLDR
The ability to easily program sequence-specific DNA targeting and cleavage by CRISPR-Cas components, as demonstrated for Cas9 and Cpf1, allows for the application of CRISpr- Cas components as highly effective tools for genetic engineering and gene regulation in a wide range of eukaryotes and prokaryotes.
Abstract
Adaptive immunity had been long thought of as an exclusive feature of animals. However, the discovery of the CRISPR-Cas defense system, present in almost half of prokaryotic genomes, proves otherwise. Because of the everlasting parasite-host arms race, CRISPR-Cas has rapidly evolved through horizontal transfer of complete loci or individual modules, resulting in extreme structural and functional diversity. CRISPR-Cas systems are divided into two distinct classes that each consist of three types and multiple subtypes. We discuss recent advances in CRISPR-Cas research that reveal elaborate molecular mechanisms and provide for a plausible scenario of CRISPR-Cas evolution. We also briefly describe the latest developments of a wide range of CRISPR-based applications.

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Citations
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Journal ArticleDOI

Diversity, classification and evolution of CRISPR-Cas systems

TL;DR: Comparative analysis of the effector complexes indicates that Class 2 systems evolved from mobile genetic elements on multiple, independent occasions and type VI systems are the first among the CRISPR-Cas variants to exclusively target RNA.
Journal ArticleDOI

Diversity and evolution of class 2 CRISPR-Cas systems

TL;DR: A comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes is presented, evolutionary scenarios for the independent origin of different class 2 CRISPR–Cas systems from mobile genetic elements are outlined, and an amended classification and nomenclature of CRISpr–Cas is proposed.
Journal ArticleDOI

The Biology of CRISPR-Cas: Backward and Forward.

TL;DR: The biology of the diverse CRISpr-Cas systems and the major progress achieved in recent years in understanding the underlying mechanisms of the three stages of CRISPR-Cas immunity are reviewed.
References
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Journal ArticleDOI

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

TL;DR: This study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
Journal ArticleDOI

Multiplex Genome Engineering Using CRISPR/Cas Systems

TL;DR: The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage as discussed by the authors.
Journal ArticleDOI

RNA-Guided Human Genome Engineering via Cas9

TL;DR: The type II bacterial CRISPR system is engineer to function with custom guide RNA (gRNA) in human cells to establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Journal ArticleDOI

CRISPR provides acquired resistance against viruses in prokaryotes

TL;DR: It is found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences, and CRISPR provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.
Journal ArticleDOI

Development and applications of CRISPR-Cas9 for genome engineering.

TL;DR: In this paper, the authors describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions, and highlight challenges and future directions.
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