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Record W2997388470 · doi:10.1101/gr.255414.119

Versatile and robust genome editing with <i>Streptococcus thermophilus</i> CRISPR1-Cas9

2020· article· en· W2997388470 on OpenAlex
Daniel Agudelo, Sophie Carter, Minja Velimirovic, Alexis Duringer, Jean-François Rivest, Sébastien Levesque, Jérémy Loehr, Mathilde Mouchiroud, Denis Cyr, Paula J. Waters, Mathieu Laplante, Sylvain Moineau, Adeline Goulet, Yannick Doyon

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueGenome Research · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversité LavalInstitut universitaire de cardiologie et de pneumologie de QuébecCentre hospitalier de l'Université LavalCentre Hospitalier Universitaire de SherbrookeCentre hospitalier universitaire de Québec
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchFonds de Recherche du Québec - SantéFondation du Grand défi Pierre LavoieNational Institutes of HealthAgence Nationale de la RechercheUniversity of California, San FranciscoNational Institute of General Medical SciencesBanting Research Foundation
KeywordsBiologyCRISPRCas9Genome editingComputational biologyStreptococcus thermophilusGeneticsGenomeCytosineDNAGeneBacteria

Abstract

fetched live from OpenAlex

Targeting definite genomic locations using CRISPR-Cas systems requires a set of enzymes with unique protospacer adjacent motif (PAM) compatibilities. To expand this repertoire, we engineered nucleases, cytosine base editors, and adenine base editors from the archetypal Streptococcus thermophilus CRISPR1-Cas9 (St1Cas9) system. We found that St1Cas9 strain variants enable targeting to five distinct A-rich PAMs and provide a structural basis for their specificities. The small size of this ortholog enables expression of the holoenzyme from a single adeno-associated viral vector for in vivo editing applications. Delivery of St1Cas9 to the neonatal liver efficiently rewired metabolic pathways, leading to phenotypic rescue in a mouse model of hereditary tyrosinemia. These robust enzymes expand and complement current editing platforms available for tailoring mammalian genomes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.584
Threshold uncertainty score0.564

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.041
GPT teacher head0.330
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it