Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
Генная терапия гемопоэтическими стволовыми клетками с использованием лентивирусного вектора у пациентов с синдромом Вискотта—Олдрича
2013-07-12
SCID: 54.1/u584auds
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Wiskott-Aldrich syndromeex vivo gene transferhematopoietic stem cellslentiviral gene therapyproto-oncogene integration
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Abstract (AI)
Next-Generation Gene Therapy Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety.
Key Findings
1
Longer follow-up is required to further validate the treatment’s long-term efficacy and safety.
2
No evidence was found of lentiviral vector integration near proto-oncogenes, addressing a major gene-therapy safety concern.
3
Optimized lentiviral vectors successfully introduced functional WAS genes into patients’ hematopoietic stem cells ex vivo.
4
The therapy halted disease progression in most patients with Wiskott-Aldrich syndrome.
5
Treated patients demonstrated stable engraftment of transduced hematopoietic stem cells and high expression of functional WAS genes for up to 2 years.
Research Object
Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome
Research Subject
Stable engraftment and functional WAS gene expression, along with treatment efficacy and lentiviral integration safety
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2013-07-12
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