Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing

Resistance of gRNA to ubiquitous ribonucleases is required for CRISPR-Cas9-based therapeutics. Here, the authors explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor, and identify modified versions that are more potent and stable than their unmodified counterparts...

Full description

Bibliographic Details
Main Authors: Aamir Mir, Julia F. Alterman, Matthew R. Hassler, Alexandre J. Debacker, Edward Hudgens, Dimas Echeverria, Michael H. Brodsky, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer
Format: Article
Language:English
Published: Nature Publishing Group 2018-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-018-05073-z
id doaj-b945b146d35544ef9d5a4a30d633c3c0
record_format Article
spelling doaj-b945b146d35544ef9d5a4a30d633c3c02021-05-11T10:02:11ZengNature Publishing GroupNature Communications2041-17232018-07-01911910.1038/s41467-018-05073-zHeavily and fully modified RNAs guide efficient SpyCas9-mediated genome editingAamir Mir0Julia F. Alterman1Matthew R. Hassler2Alexandre J. Debacker3Edward Hudgens4Dimas Echeverria5Michael H. Brodsky6Anastasia Khvorova7Jonathan K. Watts8Erik J. Sontheimer9RNA Therapeutics Institute, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolRNA Therapeutics Institute, University of Massachusetts Medical SchoolResistance of gRNA to ubiquitous ribonucleases is required for CRISPR-Cas9-based therapeutics. Here, the authors explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor, and identify modified versions that are more potent and stable than their unmodified counterparts in editing human cells.https://doi.org/10.1038/s41467-018-05073-z
collection DOAJ
language English
format Article
sources DOAJ
author Aamir Mir
Julia F. Alterman
Matthew R. Hassler
Alexandre J. Debacker
Edward Hudgens
Dimas Echeverria
Michael H. Brodsky
Anastasia Khvorova
Jonathan K. Watts
Erik J. Sontheimer
spellingShingle Aamir Mir
Julia F. Alterman
Matthew R. Hassler
Alexandre J. Debacker
Edward Hudgens
Dimas Echeverria
Michael H. Brodsky
Anastasia Khvorova
Jonathan K. Watts
Erik J. Sontheimer
Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
Nature Communications
author_facet Aamir Mir
Julia F. Alterman
Matthew R. Hassler
Alexandre J. Debacker
Edward Hudgens
Dimas Echeverria
Michael H. Brodsky
Anastasia Khvorova
Jonathan K. Watts
Erik J. Sontheimer
author_sort Aamir Mir
title Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
title_short Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
title_full Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
title_fullStr Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
title_full_unstemmed Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
title_sort heavily and fully modified rnas guide efficient spycas9-mediated genome editing
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2018-07-01
description Resistance of gRNA to ubiquitous ribonucleases is required for CRISPR-Cas9-based therapeutics. Here, the authors explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor, and identify modified versions that are more potent and stable than their unmodified counterparts in editing human cells.
url https://doi.org/10.1038/s41467-018-05073-z
work_keys_str_mv AT aamirmir heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT juliafalterman heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT matthewrhassler heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT alexandrejdebacker heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT edwardhudgens heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT dimasecheverria heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT michaelhbrodsky heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT anastasiakhvorova heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT jonathankwatts heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
AT erikjsontheimer heavilyandfullymodifiedrnasguideefficientspycas9mediatedgenomeediting
_version_ 1721448867682058240