Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: Base editing of hematopoietic stem cells rescues sickle cell disease in mice

PROVIDER: PRJNA725249 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR14327300_1.fastq.gz	Fastqsanger.gz
	SRR14327300_2.fastq.gz	Fastqsanger.gz
	SRR14329400.fastq.gz	Fastqsanger.gz
	SRR14329500.fastq.gz	Fastqsanger.gz
	SRR14327301_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 352

Similar Datasets

Homo sapiens

Project description:Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice

| PRJNA915048 | ENA

Editing the Sickle Cell Disease Mutation in Primary Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates

Project description:Site-specific correction of a point mutation causing a monogenic disease in autologous hematopoietic stem and progenitor cells (HSPCs) can be used as a treatment of inherited disorders of the blood cells. Sickle Cell Disease (SCD) is an ideal model to investigate the potential use of gene editing to transvert a single point mutation at the β-globin locus (HBB). We compared the activity of ZFNs and CRISPR/Cas9 for editing and homologous donor templates delivered as single-stranded oligodeoxynucleotides (ssODN), adeno-associated virus serotype 6 (AAV6), integrase-deficient lentiviral vectors (IDLV) and adenovirus 5/35 serotype (Ad5/35) to transvert the base-pair responsible for SCD in HBB in primary human CD34+ HSPCs. We found that the ZFNs and Cas9 directed similar frequencies of nuclease activity. In vitro, AAV6 led to the highest frequencies of homology-directed repair (HDR), but levels of base-pair transversions were significantly reduced when analyzing cells in vivo in immune-deficient mouse xenografts, with similar frequencies achieved with either AAV6 or ssODN. AAV6 also caused significant impairment of colony-forming progenitors and human cell engraftment. Gene correction in engrafting hematopoietic stem cells may be limited by the capacity of the cells to mediate HDR, suggesting additional manipulations may be needed for high efficiency gene correction in HSPCs

2019-05-18 | GSE131387 | GEO

Adenine Base Editing of Hematopoietic Stem Cells Rescues T-Cell Development for CD3δ Severe Combined Immune Deficiency

Project description:Adenine Base Editing of Hematopoietic Stem Cells Rescues T-Cell Development for CD3δ Severe Combined Immune Deficiency

| PRJNA910525 | ENA

Project description:Therapeutic base editing of human hematopoietic stem cells

| PRJNA604208 | ENA

Project description:Off-target analysis in base edited hematopoietic stem progenitor cells (HSPCs) from patients with sickle cell disease

| PRJNA1237884 | ENA

Home sapiens and Mus musculus

Project description:In vivo HSC prime editing rescues Sickle Cell Disease in a mouse model

| PRJNA869109 | ENA

Project description:Therapeutic adenine base editing of human hematopoietic stem cells

| PRJNA892449 | ENA

Potent and uniform fetal hemoglobin induction via base editing [Cut & Run]

Project description:Genetic manipulations to increase fetal hemoglobin (HbF, α2γ2) in postnatal red blood cells (RBCs) can alleviate β-thalassemia and sickle cell disease. We compared five strategies in CD34+ hematopoietic stem and progenitor cells, using either Cas9 nuclease, which creates uncontrolled indel mixtures, or adenine base editors (ABE), which generate more precise nucleotide changes. The most potent modification was ABE generation of γ-globin (HBG1/HBG2) −175 A>G, which creates a promoter binding motif for the transcriptional activator TAL1. In erythroid colonies with >87.5% on-target edits, those with −175 A>G expressed 81 ± 7% HbF, versus 17 ± 11% in unedited controls. In comparison, HbF levels were lower and more variable in erythroid cells modified with either of two Cas9 nuclease strategies with similar editing efficiencies, being 32 ± 19% when a BCL11A repressor binding motif in the γ-globin promoter was targeted and 52 ± 13% when the +58 BCL11A erythroid enhancer was targeted. Contrary to currently accepted models of γ-globin regulation, HbF levels varied significantly with different Cas9 indels that disrupted the γ-globin promoter BCL11A binding motif. The −175 A>G base edit also induced HbF more potently than did the Cas9 nuclease approaches in RBCs generated after transplantation of modified normal or SCD patient CD34+ cells into mice. Our data suggest a strategy for potent, uniform induction of HbF and provide insights into γ-globin gene regulation. More generally, we demonstrate that diverse indels generated by Cas9 nuclease can cause unexpected variations in biological outcomes that can be circumvented by base editing, with important implications for therapeutic gene editing efforts.

2023-04-28 | GSE228819 | GEO

Project description:High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease

| PRJNA1166861 | ENA

Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease

Project description:The pre-clinical efficacy and safety data support the initiation of a phase I/II clinical trial for β-globin gene correction in patient-derived hematopoietic stem cells for the treatment of sickle cell disease.

2021-05-16 | GSE163912 | 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