Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1209104 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A truncated reverse transcriptase enhances prime editing by split AAV vectors
| PRJNA846287 | ENA
Project description:Prime editing is a novel genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct a wide variety of genetic defects.
We succeeded in efficient prime editing and functional recovery of disease-causing mutations in patient-derived liver and intestinal stem cell organoids. Whole genome sequencing of did not detect off-target mutations or a mutational signature induced by prime editing.
| EGAS00001004611 | EGA
Project description:Prime editors (PEs) can mediate versatile genome editing but their efficiency remains low. Here, we developed spegRNA by introducing same-sense mutations at proper positions in the reverse-transcription template of pegRNA to increase PE’s single-base editing efficiency or apegRNA by altering the pegRNA secondary structure to increase PE’s indel-editing efficiency . When used in PE3 and PE5, the efficiencies of sPE3, aPE3, sPE5 and aPE5 were all enhanced significantly.
2022-03-10 | GSE197730 | GEO
Project description:DNA hypermethylation enhanced telomerase reverse transcriptase expression in human induced pluripotent stem cells
| PRJNA389403 | ENA
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
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.
2023-07-18 | GSE220765 | GEO
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.
2023-07-18 | GSE220763 | GEO