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Type II CRISPR-Cas System Nucleases: A Pipeline for Prediction and In Vitro Characterization

Vasileva, A A ; Aliukas, S A ; Selkova, P A LU ; Arseniev, A N ; Chernova, V E ; Musharova, O S ; Klimuk, E I ; Khodorkovskii, M A and Severinov, K V (2023) In Molekuliarnaia biologiia 57(3). p.550-562
Abstract

The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are complementary to guide RNA sequences. Despite the wide range of characterized Cas9s, the search for new Cas9 variants remains an important task, since the available Cas9 editors have several limitations. This paper presents a workflow for the search for and subsequent characterization of new Cas9 nucleases developed in our laboratory. Detailed... (More)

The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are complementary to guide RNA sequences. Despite the wide range of characterized Cas9s, the search for new Cas9 variants remains an important task, since the available Cas9 editors have several limitations. This paper presents a workflow for the search for and subsequent characterization of new Cas9 nucleases developed in our laboratory. Detailed protocols describing the bioinformatical search, cloning, and isolation of recombinant Cas9 proteins, testing for the presence of nuclease activity in vitro, and determining the PAM sequence, which is required for recognition of DNA targets, are presented. Potential difficulties that may arise, as well as ways to overcome them, are considered.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
CRISPR-Cas Systems, CRISPR-Associated Protein 9/genetics, Gene Editing/methods, Bacteria/genetics, Recombinant Proteins/genetics, DNA/metabolism
in
Molekuliarnaia biologiia
volume
57
issue
3
pages
550 - 562
external identifiers
  • scopus:85163904060
  • pmid:37326060
ISSN
0026-8984
DOI
10.1134/S0026893323030147
language
English
LU publication?
no
id
1f6b8382-f726-4bb7-826c-f14c4c0c385e
date added to LUP
2026-01-29 10:08:40
date last changed
2026-01-30 04:01:47
@article{1f6b8382-f726-4bb7-826c-f14c4c0c385e,
  abstract     = {{<p>The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are complementary to guide RNA sequences. Despite the wide range of characterized Cas9s, the search for new Cas9 variants remains an important task, since the available Cas9 editors have several limitations. This paper presents a workflow for the search for and subsequent characterization of new Cas9 nucleases developed in our laboratory. Detailed protocols describing the bioinformatical search, cloning, and isolation of recombinant Cas9 proteins, testing for the presence of nuclease activity in vitro, and determining the PAM sequence, which is required for recognition of DNA targets, are presented. Potential difficulties that may arise, as well as ways to overcome them, are considered.</p>}},
  author       = {{Vasileva, A A and Aliukas, S A and Selkova, P A and Arseniev, A N and Chernova, V E and Musharova, O S and Klimuk, E I and Khodorkovskii, M A and Severinov, K V}},
  issn         = {{0026-8984}},
  keywords     = {{CRISPR-Cas Systems; CRISPR-Associated Protein 9/genetics; Gene Editing/methods; Bacteria/genetics; Recombinant Proteins/genetics; DNA/metabolism}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{550--562}},
  series       = {{Molekuliarnaia biologiia}},
  title        = {{Type II CRISPR-Cas System Nucleases: A Pipeline for Prediction and In Vitro Characterization}},
  url          = {{http://dx.doi.org/10.1134/S0026893323030147}},
  doi          = {{10.1134/S0026893323030147}},
  volume       = {{57}},
  year         = {{2023}},
}