Combined Ultrafiltration-Transduction in a Hollow-Fiber Bioreactor Facilitates Retrovirus-Mediated Gene Transfer into Peripheral Blood Lymphocytes from Patients with Mucopolysaccharidosis Type II

Pan, Dao; Shankar, Raji A.; Stroncek, David F.; Whitley, Chester B.

doi:10.1089/10430349950016537

Cited by 10 publications

(6 citation statements)

References 52 publications

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“…Some of these difficulties could be circumvented by the use of improved viral vectors, virus purification conditions [72, 73, 74], transduction procedures, and viral packaging cell lines [75, 76, 77, 78, 79, 80]. Moreover, the expansion, transduction, and selection of target cells, like BM stem cells, in vitro have been facilitated by the use of specific cell culture conditions and selectable markers [a].…”

Section: Gene Transfer and Gene Therapy For Lysosomal Storage Diseasementioning

confidence: 99%

Gene Transfer Strategies for Correction of Lysosomal Storage Disorders

d’Azzo¹

2003

Acta Haematol

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Lysosomal storage diseases (LSDs) represent a large group of monogenic disorders of metabolism, which affect approximately 1 in 5,000 live births. LSDs result from a single or multiple deficiency of specific lysosomal hydrolases, the enzymes responsible for the luminal catabolization of macromolecular substrates. The consequent accumulation of undigested metabolites in lysosomes leads to polysystemic dysfunction, including progressive neurologic deterioration, mental retardation, visceromegaly, blindness, and early death. In general, the residual amount of functional enzyme in lysosomes determines the severity and age at onset of the clinical symptoms, implying that even modest increases in enzyme activity might affect a cure. A key feature on which therapy for LSDs is based is the ability of soluble enzyme precursors to be secreted by one cell type and reinternalize by neighboring cells via receptor-mediated endocytosis and routed to lysosomes, where they function normally. In principle, somatic gene therapy could be the preferred treatment for LSDs if the patient’s own cells could be genetically modified in vitro or in vivo to constitutively express high levels of the correcting enzyme and become the source of the enzyme in the patient. Both ex vivo and in vivo gene transfer methods have been experimented with for gene therapy of lysosomal disorders. Several of these methods have proved efficient for the transfer of genetic material into deficient cells in culture and reconstitution of enzyme activity. However, the same methods applied to humans or animal models have been giving inconsistent results, the bases of which are not fully understood. A broader knowledge of disease pathogenesis, facilitated by available, faithful animal models of LSDs, coupled to the development of better gene transfer systems as well as the understanding of vector host interactions will make somatic gene therapy for these devastating and complex diseases the most suitable therapeutic approach.

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Section: Gene Transfer and Gene Therapy For Lysosomal Storage Diseasementioning

confidence: 99%

Gene Transfer Strategies for Correction of Lysosomal Storage Disorders

d’Azzo¹

2003

Acta Haematol

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“…CHO (Chinese‐hamster ovary) cells [28–30], murine erythroleukaemia cells [31], mouse mammary tumour cells S115 [32], human prostate carcinoma cells LNCaP (human prostate carcinoma cells) [33], BHK‐21 (baby‐hamster kidney 21) cells producing a chimaeric human monoclonal antibody [34] and patented human hepatoblastoma C3A cells [35]. Other cell lines grown in an HFB include human T‐lymphocytes for cytokine production [36], human lymphocytes for gene therapy [37] and gene transfer [38] and human hepatocellular liver carcinoma cell line Hep G2 [39]. HFBs were used for retroviral vector production [40,41], for co‐culturing rat endothelial and rat glial cells to simulate the blood/brain barrier [42] and to create artificial organs like liver [43–45], kidney [43] and pancreas [46].…”

Section: Introductionmentioning

confidence: 99%

Recombinant‐protein production in insect cells utilizing a hollow‐fibre bioreactor

Baxter

Panarello

Ajith

et al. 2006

Biotech and App Biochem

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Here, we demonstrate for the first time that the hollow-fibre bioreactor is an excellent tool for the production of Drosophila-expressed recombinant proteins. Using the example of the soluble extracellular portion of the human IL-5 (interleukin 5) receptor alpha expression in S2 (Schneider's Drosophila melanogaster cell line 2) cells, we found that it is possible to produce multi-milligram amounts of functional recombinant protein continuously for several months on a laboratory scale with minimal maintenance requirements. The insect cells grow to high density and express concentrated functional recombinant protein in a small volume, simplifying and economizing downstream purification.

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“…In the past, such systems have been used for production of industrial and clinical‐grade reagents such as monoclonal antibodies 24, cell lines 25, 26, and other biologics destined for pharmacological applications 27, 28. In our previous work 29, we have demonstrated that an HBS could be used to culture and transduce human primary peripheral blood lymphocytes (PBL) in clinically useful quantities (up to 10 10 primary PBL). Moreover, gene transfer efficiency was improved (up to 57%) in these large amounts of PBL without the use of centrifugation, fibronectin, or other special manipulations.…”

Section: Introductionmentioning

confidence: 99%