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| Status |
Public on Oct 06, 2023 |
| Title |
Integrome signatures of lentiviral gene therapy for SCID-X1 patients |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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.
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| 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
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| Department |
Department of Computational Biology
|
| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE163083 |
Integrome signatures of lentiviral gene therapy for SCID-X1 patients |
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| Relations |
| BioProject |
PRJNA684622 |
| SRA |
SRP297716 |
