Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

No observable guide-RNA-independent off-target mutation induced by prime editor [TargetSeq]

ABSTRACT: Prime editor (PE) has been recently developed to induce efficient and precise on-target editing, whereas its guide RNA (gRNA)-independent off-target effects remain unknown. Here, we used whole-genome and whole-transcriptome sequencing to determine gRNA-independent off-target mutations in cells expanded from single colonies, in which PE generated precise editing at on-target sites. We found that PE triggered no observable gRNA-independent off-target mutation genome-wide or transcriptome-wide in transfected human cells, highlighting its high specificity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178112 | GEO | 2022/02/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

No observable guide-RNA-independent off-target mutation induced by prime editor [RNA-Seq]

Project description:Prime editor (PE) has been recently developed to induce efficient and precise on-target editing, whereas its guide RNA (gRNA)-independent off-target effects remain unknown. Here, we used whole-genome and whole-transcriptome sequencing to determine gRNA-independent off-target mutations in cells expanded from single colonies, in which PE generated precise editing at on-target sites. We found that PE triggered no observable gRNA-independent off-target mutation genome-wide or transcriptome-wide in transfected human cells, highlighting its high specificity.

2022-02-03 | GSE178111 | GEO

No observable guide-RNA-independent off-target mutation induced by prime editor

Project description:No observable guide-RNA-independent off-target mutation induced by prime editor

| PRJNA737401 | ENA

No observable guide-RNA-independent off-target mutation induced by prime editor [TargetSeq]

Project description:No observable guide-RNA-independent off-target mutation induced by prime editor [TargetSeq]

| PRJNA737412 | ENA

No observable guide-RNA-independent off-target mutation induced by prime editor [RNA-Seq]

Project description:No observable guide-RNA-independent off-target mutation induced by prime editor [RNA-Seq]

| PRJNA737408 | ENA

AI-generated MLH1 small binder improves prime editing efficiency

Project description:The prime editing (PE) system consists of a Cas9 nickase fused to a reverse transcriptase, which introduces precise edits into the target genomic region guided by a prime editing guide RNA. However, PE efficiency is limited by mismatch repair. To overcome this limitation, transient expression of a dominant-negative MLH1 (MLH1dn) has been used to inhibit key components of mismatch repair. Here, we designed a de novo MLH1 small binder (MLH1-SB) that binds to the dimeric interface of MLH1 and PMS2 using RFdiffusion and AlphaFold 3. The compact size of MLH1-SB enabled its integration into existing PE architectures via 2A systems, creating a novel PE-SB platform. The PE7-SB system significantly improved PE efficiency, achieving an 18.8-fold increase over PEmax and a 2.5-fold increase over PE7 in HeLa cells, as well as a 3.4-fold increase over PE7 in mice. This study highlights the potential of generative AI in advancing genome editing technology.

2025-04-07 | GSE293633 | GEO

Improved split prime editors enable efficient in vivo genome editing.

Project description:Prime editor (PE) is a precise genome-editing tool capable of all possible base conversions, as well as insertions and deletions without DSBs or donor DNA. The efficient delivery of PE in vivo is critical for realizing its full potential in disease modeling and therapeutic correction. Although PE has been divided into two halves and delivered using dual adeno-associated viruses (AAVs), editing efficiency at different gene loci varies among split sites, and efficient split sites within Cas9 nickase are limited. In this study, by screening multiple split sites, we demonstrated a series of efficient split site when delivering PE by dual-AAV. Additionally, we utilized a feature reported by others recently that RNase could be detached from the Cas9n and designed split sites in the first half of Cas9n. To test the editing efficiency in vivo, a novel dual-AAV split-ePE3 was packaged in AAV9 and delivered via tail vein injection in mice, achieving 24.4% precise genome editing 3 weeks post-injection. Our findings establish an alternative split-PE architecture that could achieve robust gene editing efficiency, facilitating the potential utility both in model organisms and as a therapeutic modality.

2025-03-15 | GSE291960 | GEO

Improved split prime editors enable efficient in vivo genome editing

2024-12-01 | GSE270813 | GEO

Improved split prime editors enable efficient in vivo genome editing [Amplicon_Seq_in_vitro]

2024-12-01 | GSE270854 | GEO

Easy-Prime: a machine learning–based prime editor design tool

Project description:We developed ML-based methods to optimize PE design

2021-07-26 | GSE175955 | GEO

Genotoxic effects of base and prime editing in human hematopoietic stem cells [NHEJ_BaseE_MultiLocus]

Project description:Emerging base and prime editing may provide safer and more precise genetic engineering than nuclease-based approaches bypassing the dependence on DNA double strand breaks (DSBs). However, little is known about cellular responses and genotoxicity. Here, we comparatively assessed state-of-the-art base and prime editors (B/PE) versus Cas9 in human hematopoietic stem/progenitor cells (HSPCs). BE and PE induced detrimental transcriptional responses constraining editing efficiency and/or HSPC repopulation in xenotransplants, albeit to a lesser extent than Cas9. DNA DSBs and their genotoxic byproducts, including deletions and translocations, were less frequent but not abrogated by BE and PE, particularly for cytidine BE due to suboptimal inhibition of base excision repair. Tailoring timing and B/PE expression enabled highly efficient and precise editing of long-term repopulating HSPCs. However, we uncovered a genome-wide effect of BEs on the mutational landscape of HSPCs, raising concerns for a potential genotoxic impact and calling for further investigations and improvements in view of clinical application.

2023-08-02 | GSE239852 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data