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Series GSE163082 Query DataSets for GSE163082
Status Public on Oct 06, 2023
Title Integrome signatures of lentiviral gene therapy for SCID-X1 patients
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Lentiviral vector (LV)-based gene therapy holds promise for a broad range of diseases. Analyzing more than 280,000 vector integration sites (VISs) in 273 samples from 10 patients with X-linked severe combined immunodeficiency (SCID-X1), we discovered shared LV integrome signatures in 9 out of 10 patients in relation to the genomics, epigenomics, and 3D structure of the human genome. VISs were enriched in the nuclear sub-compartment A1 and integrated into super-enhancers close to nuclear pore complexes. These signatures were validated in T cells transduced with an LV encoding a CD19-specific chimeric antigen receptor. Intriguingly, the one patient whose VISs deviated from the identified integrome signatures had a distinct clinical course. Comparison of LV and gamma retrovirus integromes regarding their 3D genome signatures, identified differences that might explain the lower risk of insertional mutagenesis in LV-based gene therapy. Our findings suggest that LV integrome signatures, shaped by common features such as genome organization, may impact the efficacy of LV-based cellular therapies.
 
Overall design To confirm VIS signatures, we performed single-cell profilng for bone marrow samples of two SCID-X1 patients 18 months after gene transfusion.
 
Contributor(s) Yan K, Gottschalk S, Yu J
Citation(s) 37801507
Submission date Dec 11, 2020
Last update date Oct 18, 2023
Contact name Jiyang Yu
Organization name St Jude Children's Research Hospital
Department Department of Computational Biology
Street address 262 Danny Thomas Pl
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (2)
GSM4971778 P1_bone_marrow [scATAC-seq]
GSM4971779 P6_bone_marrow [scATAC-seq]
This SubSeries is part of SuperSeries:
GSE163083 Integrome signatures of lentiviral gene therapy for SCID-X1 patients
Relations
BioProject PRJNA684626
SRA SRP297715

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Supplementary file Size Download File type/resource
GSE163082_RAW.tar 255.6 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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