Progress and Prospects: Gene Therapy Clinical Trials (Part 1)

Alton, Eric W.F.W.

doi:10.1038/sj.gt.3303001

Cited by 100 publications

(22 citation statements)

References 50 publications

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“…Treatment of those patients without HLA-matched donors remains problematic. In addition to haematopoietic stem cell (HSC) based therapy, refractory infections in CGD patients can be successfully treated using repeated infusions of functional allogeneic neutrophils, although this strategy often results in exaggerated inflammation and allo-immunisation[11]–[14]. In this study, we provide a proof-of-principle that iPSC technology can provide a valuable platform for investigating gene therapeutic approaches in CGD.…”

Section: Introductionmentioning

confidence: 98%

Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells

Mukherjee¹,

Santilli²,

Blundell³

et al. 2011

PLoS ONE

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Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91phox is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils.

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Section: Introductionmentioning

confidence: 98%

Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells

Mukherjee¹,

Santilli²,

Blundell³

et al. 2011

PLoS ONE

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“…Thus, gene therapy has the potential to treat inherited diseases including cystic fibrosis [2, 3], muscular dystrophy [3–5] and severe combined immunodeficiency (SCID) [3], as well as acquired diseases such as cancers [6], cardiovascular diseases and viral infections [7, 8]. This technology has yet to deliver on its promise, however, due in large part to the lack of safe and efficient means of delivering therapeutic genes [9].…”

Section: Introductionmentioning

confidence: 99%

Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors

Keswani

Shu

Pack

2014

Journal of Controlled Release

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Recombinant retroviruses provide highly efficient gene delivery and the potential for sustained gene expression, but suffer from significant disadvantages including low titer, expensive production, poor stability and limited flexibility for modification of tropism. In contrast, polymer-based vectors are more robust and allow cell- and tissue-specific delivery via conjugation of ligands, but are comparatively inefficient. The design of hybrid gene delivery agents comprising both virally derived and synthetic materials (nanobiovectors) represents a promising approach to development of safe and efficient gene therapy vectors. Non-infectious murine leukemia virus-like particles (M-VLP) were electrostatically complexed with chitosan (χ) to replace the function of the viral envelope protein. At optimal fabrication conditions and compositions, ranging from 6–9 µg chitosan/109 M-VLP at 10 × 109 M-VLP/ml to 40 µg chitosan /109 M-VLP at 2.5 × 109 M-VLP/ml, χ/M-VLP were ~300–350 nm diameter and exhibited efficient transfection similar to amphotropic MLV vectors. In addition, these nanobiovectors were non-cytotoxic and provided sustained transgene expression for at least three weeks in vitro. This combination of biocompatible synthetic agents with inactive viral particles to form a highly efficient hybrid vector is a significant extension in the development of novel gene delivery platforms.

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“…Gene therapy has emerged as a powerful tool to regulate biological functions in diseased tissues and to treat cancers [14], [15]. Oncolytic viruses not only have capacity to express therapeutic genes in tumor cells but also can be used as a direct tumor-destruction medicament.…”

Section: Introductionmentioning

confidence: 99%

Combined Therapy with Cytokine-Induced Killer Cells and Oncolytic Adenovirus Expressing IL-12 Induce Enhanced Antitumor Activity in Liver Tumor Model

Yang

Zhang

et al. 2012

PLoS ONE

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Both adoptive immunotherapy and gene therapy hold a great promise for treatment of malignancies. However, these strategies exhibit limited anti-tumor activity, when they are used alone. In this study, we explore whether combination of cytokine-induced killer (CIK) adoptive immunotherapy with oncolytic adenovirus-mediated transfer of human interleukin-12 (hIL-12) gene induce the enhanced antitumor potency. Our results showed that oncolytic adenovirus carrying hIL-12 (AdCN205-IL12) could produce high levels of hIL-12 in liver cancer cells, as compared with replication-defective adenovirus expressing hIL-12 (Ad-IL12). AdCN205-IL12 could specifically induce cytotoxocity to liver cancer cells. Combination of CIK cells with AdCN205-IL12 could induce higher antitumor activity to liver cancer cells in vitro than that induced by either CIK or AdCN205-IL12 alone, or combination of CIK and control vector AdCN205-GFP. Furthermore, treatment of the established liver tumors with the combined therapy of CIK cells and AdCN205-IL12 resulted in tumor regression and long-term survival. High level expression of hIL-12 in tumor tissues could increase traffic of CIK cells to tumor tissues and enhance their antitumor activities. Our study provides a novel strategy for the therapy of cancer by the combination of CIK adoptive immunotherapy with oncolytic adenovirus-mediated transfer of immune stimulatory molecule hIL-12.

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Progress and Prospects: Gene Therapy Clinical Trials (Part 1)

Cited by 100 publications

References 50 publications

Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells

Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells

Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors

Combined Therapy with Cytokine-Induced Killer Cells and Oncolytic Adenovirus Expressing IL-12 Induce Enhanced Antitumor Activity in Liver Tumor Model

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