Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.
The occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients is described and a general toxicity of endogenous gammaretroviral enhancer elements is highlighted.
High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an…
It is demonstrated that lentiviral vectors are highly effective for gene transfer to human HSC, and that SFFV regulatory sequences can be successfully incorporated to enhance the long-term expression of a transgene in primary human hematopoietic cells in vivo.
Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector
Hematopoietic Stem Cell Gene Therapy for Adenosine Deaminase–Deficient Severe Combined Immunodeficiency Leads to Long-Term Immunological Recovery and Metabolic Correction
Two new studies provide clinical support for treatment options that may allow SCID patients without matched donors to live relatively normal lives as well and support the development of new safer and more efficient vectors for this and other kinds of gene therapy.
Long-Term Persistence of a Polyclonal T Cell Repertoire After Gene Therapy for X-Linked Severe Combined Immunodeficiency
Two new studies provide clinical support for treatment options that may allow SCID patients without matched donors to live relatively normal lives and support the development of new safer and more efficient vectors for this and other kinds of gene therapy.
Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.
High-level transduction and gene expression in hematopoietic repopulating cells using a human imunodeficiency virus type 1-based lentiviral vector containing an internal spleen focus forming virus…
A vesicular stomatitis virus G envelope protein (VSV-G)-pseudotyped human immunodeficiency virus type 1 (HIV-1) lentiviral-based vector system is used to transduce cord blood (CB) CD34+ cells over a limited time period and significant gene marking was observed in engrafted human lymphoid, myeloid, and progenitor cells in all transplanted Severe Combined Immunodeficient mice.
In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothelium and retinal pigment epithelium
Efficient in vivo gene transfer into cells of the corneal endothelium and retinal pigment epithelium by lentiviral vectors may offer a valuable approach to the treatment of disorders of the Cornea and outer retina.
Biochemical correction of X-CGD by a novel chimeric promoter regulating high levels of transgene expression in myeloid cells.
In a murine model of stem cell gene therapy for X-CGD, the chimeric vector resulted in high levels of gp91(phox) expression in committed myeloid cells and granulocytes, and restored normal NADPH-oxidase activity, suggesting that the Chimeric promoter will have utility for gene therapy of myeloids lineage disorders such as CGD.
Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo.
The divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation.