Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Correction of a Factor VIII genomic inversion with designer recombinases

ABSTRACT: Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct a 140 kb int1h inversion frequently found in patients diagnosed with Hemophilia A. With the use of directed molecular evolution, we developed a linked heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from int1h patient derived iPSCs, resulted in prominent correction of the inversion and restored Factor VIII mRNA expression. Our data suggest that the development of designer-recombinases represent an efficient and specific mean towards treatment of large gene inversions causing monogenic diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159492 | GEO | 2021/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Correction of a Factor VIII genomic inversion with designer recombinasesÃ¯Â»Â¿

Project description:Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in 12% correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.

| EGAS00001005496 | EGA

Correction of a Factor VIII genomic inversion with designer recombinases

Project description:Correction of a Factor VIII genomic inversion with designer recombinases

| PRJNA669049 | ENA

Zinc finger DNA-binding conditioned site-specific recombination

Project description:Programmable nucleases and designer-recombinases are prominent genome editing tools that hold great potential for the treatment of human genetic disorders. However, both of these tools alone are not optimal for clinical applications. We present an approach that combines the ease of targeting of programmable nucleases with editing safety and accuracy of site-specific recombinases. We find that insertional fusions of zinc-finger DNA-binding domains (ZFDs) into the coding sequence of designer-recombinases generate conditional enzymes that are inactive, unless the ZFD binds its target site placed in the vicinity of the recombinase binding site. This induced-fit activity is transferable to a recombinase with relaxed specificity, representing the prototype of a new class of genome editing enzymes that opens exciting perspectives for flexible, seamless, and precise genome surgery.

2023-12-19 | GSE243676 | GEO

Expression data of sandwich cultured primary rat hepatocytes incubated to piperazine designer drugs

Project description:The piperazine derivatives most frequently consumed for recreational purposes are 1-benzylpiperazine (BZP), 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), and 1-(4-methoxyphenyl)piperazine (MeOPP). Currently it is unclear whether piperazine designer drugs induce mechanisms of hepatotoxicity and, if so, whether they act by a common mechanism. We performed a gene array study with rat hepatocytes incubated with the four designer drugs for 24 h in order to detail the global programme of gene expression Primary rat hepatocytes were cultured in collagen sandwich and incubated with the piperazine designer drugs. After 24 h, the RNA was extracted and the Affymetrix microarray analysis was performed.

2015-05-13 | E-GEOD-68785 | biostudies-arrayexpress

Expression differences between inversions and their progenitors in Drosophila melanogaster

Project description:Inversions have a breakpoint within a "neighbourhood" of testis expressed genes and the other breakpoint megabases away. The gene expression neighbourhood is therefore intact in the progenitor but disrupted in the inversion. 12 different inversion stocks, 3 or 4 biological replicates for each, including dye swaps.

2010-06-25 | E-GEOD-16616 | biostudies-arrayexpress

Expression differences between inversions and their progenitors in Drosophila melanogaster embryos

Project description:Inversions have a breakpoint within a "neighbourhood" of embryonically expressed genes and the other breakpoint megabases away. The gene expression neighbourhood is therefore intact in the progenitor but disrupted in the inversion. 1 progenitor stock and 1 inversion stock, 4 biological replicates for each, including 2 dye swaps.

2010-05-05 | E-GEOD-21607 | biostudies-arrayexpress

Expression differences between inversions and their progenitors in Drosophila melanogaster

Project description:Inversions have a breakpoint within a "neighbourhood" of testis expressed genes and the other breakpoint megabases away. The gene expression neighbourhood is therefore intact in the progenitor but disrupted in the inversion. Keywords: Genome variation profiling by array 12 different inversion stocks, 3 or 4 biological replicates for each, including dye swaps.

2010-12-06 | E-GEOD-15565 | biostudies-arrayexpress

A designer peptide against the EAG2-Kvβ2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma

Project description:This dataset includes the raw single-cell RNAseq data from Xenograft GBM tumor (G411)-bearing NSG mice model treated with either control peptide K59-78TAT or designer peptide K90-114TAT and raw bulk RNAseq data from GBM cell (G411)-neuron coculture model treated with either control peptide K59-78TAT or designer peptide K90-114TAT. In this project, we focused on transcriptomic alteration caused by designer peptide in tumor cells.

2023-06-25 | GSE231577 | GEO

Expression data of sandwich cultured primary rat hepatocytes incubated to piperazine designer drugs

2015-05-13 | GSE68785 | GEO

Inversion breakpoints in Drosophila

Project description:Inversion evolutionary rates might limit the experimental identification of inversion breakpoints in non-model species

| PRJEB23256 | ENA