PpCas9 from Pasteurella pneumotropica - a compact Type II-C Cas9 ortholog active in human cells.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
02 12 2020
Historique:
accepted: 16 10 2020
revised: 11 10 2020
received: 04 05 2020
pubmed: 6 11 2020
medline: 30 12 2020
entrez: 5 11 2020
Statut: ppublish

Résumé

CRISPR-Cas defense systems opened up the field of genome editing due to the ease with which effector Cas nucleases can be programmed with guide RNAs to access desirable genomic sites. Type II-A SpCas9 from Streptococcus pyogenes was the first Cas9 nuclease used for genome editing and it remains the most popular enzyme of its class. Nevertheless, SpCas9 has some drawbacks including a relatively large size and restriction to targets flanked by an 'NGG' PAM sequence. The more compact Type II-C Cas9 orthologs can help to overcome the size limitation of SpCas9. Yet, only a few Type II-C nucleases were fully characterized to date. Here, we characterized two Cas9 II-C orthologs, DfCas9 from Defluviimonas sp.20V17 and PpCas9 from Pasteurella pneumotropica. Both DfCas9 and PpCas9 cleave DNA in vitro and have novel PAM requirements. Unlike DfCas9, the PpCas9 nuclease is active in human cells. This small nuclease requires an 'NNNNRTT' PAM orthogonal to that of SpCas9 and thus potentially can broaden the range of Cas9 applications in biomedicine and biotechnology.

Identifiants

pubmed: 33152077
pii: 5957178
doi: 10.1093/nar/gkaa998
pmc: PMC7708072
doi:

Substances chimiques

RNA, Guide 0
Recombinant Proteins 0
CRISPR-Associated Protein 9 EC 3.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12297-12309

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Iana Fedorova (I)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.

Aleksandra Vasileva (A)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Polina Selkova (P)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Marina Abramova (M)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.
Saint Petersburg State University, Saint Petersburg, 199034, Russia.

Anatolii Arseniev (A)

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Georgii Pobegalov (G)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Maksim Kazalov (M)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.
Saint Petersburg State University, Saint Petersburg, 199034, Russia.

Olga Musharova (O)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.
Institute of Molecular Genetics of National Research Center "Kurchatov Institute'', Moscow, 123182, Russia.

Ignatiy Goryanin (I)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.

Daria Artamonova (D)

Skolkovo Institute of Science and Technology, Center of Life Sciences, Moscow, 121205, Russia.

Tatyana Zyubko (T)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Sergey Shmakov (S)

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

Tatyana Artamonova (T)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Mikhail Khodorkovskii (M)

Peter the Great St. Petersburg Polytechnic University, Saint Petersburg, 195251, Russia.

Konstantin Severinov (K)

Saint Petersburg State University, Saint Petersburg, 199034, Russia.
Institute of Molecular Genetics of National Research Center "Kurchatov Institute'', Moscow, 123182, Russia.

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Classifications MeSH