Long‐term expression of the human glucocerebrosidase gene in vivo after transplantation of bone‐marrow‐derived cells transformed with a lentivirus vector

Abstract

The recombinant lentiviral vector transduces HSCs that are capable of long-term gene expression in vivo. This approach is potentially useful for the treatment of patents with Gaucher disease and other lysosomal storage disorders.

Therapeutic strategies to ameliorate lysosomal storage disorders – a focus on Gaucher disease

“…Much progress has been made in the design of improved vectors including recombinant adeno-associated viral vectors [109] and HIV-1-based lentivirus vectors [110] that express human GC cDNA. Mice transplanted with lentivirus-transduced bone marrow-derived hematopoietic stem cells overexpressing human GC exhibited relatively high levels of GC activity in various tissues including bone marrow and spleen, but also the brain, 2-6 months after transplantation [111]. Although the suitability of the latter strategy to ameliorate Gaucher disease-associated symptoms in humans remains to be demonstrated, the results obtained in mice are encouraging.…”

AAV8‐mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease

“…Subsequent clinical studies showed that the transduction efficiency and engraftment of autologous stem cells from Gaucher patients occurred with insufficient efficiency for therapeutic efficacy [13]. More recently, adenoviral [14], lentiviral [15], and adeno-associated viral (AAV) vectors [16] harboring the human glucocerebrosidase (hGC) cDNA have also been evaluated, though none in a systemic animal model of Gaucher disease. Compared to other viral-based vectors, AAV vectors offer some advantages for the treatment of Gaucher disease [17][18][19].…”

Stable EGFP gene expression in C6 glioma cell line after transduction with HIV-1-based lentiviral vector

“…Lentiviral vectors drive stable, long-term transgene expression in the brain [21][22][23] , transfect adult, mature neurons and possess a larger cloning capacity than adeno-associated viral vectors (AAV). Because of its many advantages, lentiviral vectors have been proposed for treating a wide range of disease such as hematopoietic disorders and CNS diseases [24][25][26] , and for cancer therapy by delivery of anti-endostatin and anti-angiostatin gene into target tumor endothelial cells, to kill tumor cells [27,28] .…”