Trial reportNature communications2022
Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.
Trial report in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01306019 (Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Newborn screening for severe combined immunodeficiency in the NHS newborn blood spot screening programme: a systematic review.Health technology assessment (Winchester, England) · 2026Pooled it
- Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy.The New England journal of medicine · 2024Trial
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- When RNA goes off script: ensuring transcript fidelity in transgene expression.The EMBO journal · 2026Review
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- A precision gene-engineered B cell medicine producing sustained levels of active factor IX for hemophilia B therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Gene-sized DNA insertion at genomic safe harbors in human cells using a site-directed transposase.Nucleic acids research · 2025Article
- Modeling integration site data for safety assessment with MELISSA.Nature communications · 2025Article
- Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview.Regenerative therapy · 2025Review
- Transcriptomic and proteomic analysis reveals the mechanism of chicken cecum response toiScience · 2025Article
- Balancing efficacy and safety in lentiviral vector-mediated hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Innovative Approaches in Molecular Docking for the Discovery of Novel Inhibitors Against Alzheimer's Disease.Current Alzheimer research · 2025Review
- Article
- Long-term tracking of haematopoietic clonal dynamics and mutations in non-human primate undergoing transplantation of lentivirally barcoded haematopoietic stem and progenitor cells.British journal of haematology · 2024Article
- An optimized protocol for quality control of gene therapy vectors using nanopore direct RNA sequencing.Genome research · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
X-linked Severe Combined Immunodeficiency (SCID-X1) due to IL2RG mutations is potentially fatal in infancy where 'emergency' life-saving stem cell transplant may only achieve incomplete immune reconstitution following transplant. Salvage therapy SCID-X1 patients over 2 years old (NCT01306019) is a non-randomized, open-label, phase I/II clinical trial for administration of lentiviral-transduced autologous hematopoietic stem cells following busulfan (6 mg/kg total) conditioning. The primary and secondary objectives assess efficacy in restoring immunity and safety by vector insertion site analysis (VISA). In this ongoing study (19 patients treated), we report VISA in blood lineages from first eight treated patients with longer follow up found a > 60-fold increase in frequency of forward-orientated VIS within intron 3 of the High Mobility Group AT-hook 2 gene. All eight patients demonstrated emergence of dominant HMGA2 VIS clones in progenitor and myeloid lineages, but without disturbance of hematopoiesis. Our molecular analysis demonstrated a cryptic splice site within the chicken β-globin hypersensitivity 4 insulator element in the vector generating truncated mRNA transcripts from many transcriptionally active gene containing forward-oriented intronic vector insert. A two base-pair change at the splice site within the lentiviral vector eliminated splicing activity while retaining vector functional capability. This highlights the importance of functional analysis of lentivectors for cryptic splicing for preclinical safety assessment and a redesign of clinical vectors to improve safety.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.