Reconstitution of NADPH Oxidase Activity in Human X-Linked Chronic Granulomatous Disease Myeloid Cells after Stable Gene Transfer Using a Recombinant Adeno- Associated Virus 2 Vector

Li, Ling Lin; Dinauer, Mary C.

doi:10.1006/bcmd.1998.0216

Cited by 9 publications

(4 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If this proves to be the case, then lentivirus vectors may have further advantages over other viral vectors in addition to their likely benefit for transduction of more primitive non‐dividing HSC. Indeed, silencing of gp91 phox transgene expression in the myeloid X‐CGD cell line model has been reported after stable gene transfer using a recombinant adeno‐associated virus 2 (AAV) vector39. In addition, a recent paper by Zentilin et al 40.…”

Section: Discussionmentioning

confidence: 99%

Lentivirus-mediated gene transfer of gp91phox corrects chronic granulomatous disease (CGD) phenotype in human X-CGD cells

et al. 2000

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Lentivirus-mediated gene transfer of gp91phox corrects chronic granulomatous disease (CGD) phenotype in human X-CGD cells

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The plant NOX is functionally similar to neutrophil NOX. As a component of the mammalian defense system, neutrophils generate superoxide radicals via NOX (see review by Leusen et al 1996) to defend host tissue from invading pathogens (Li and Dinauer 1998;Leavey et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Strboh A homologue of NADPH oxidase regulates wound-induced oxidative burst and facilitates wound-healing in potato tubers

Kumar

Iyer

Knowles

2007

Planta

View full text Add to dashboard Cite

During 30-months of storage at 4 degrees C, potato (Solanum tuberosum L.) tubers progressively lose the ability to produce superoxide in response to wounding, resist microbial infection, and develop a suberized wound periderm. Using differentially aged tubers, we demonstrate that Strboh A is responsible for the wound-induced oxidative burst in potato and aging attenuates its expression. In vivo superoxide production and NADPH oxidase (NOX) activity from 1-month-old tubers increased to a maximum 18-24 h after wounding and then decreased to barely detectable levels by 72 h. Wounding also induced a 68% increase in microsomal protein within 18 h. These wound-induced responses were lost over a 25- to 30-month storage period. Superoxide production and NOX activity were inhibited by diphenylene iodonium chloride, a specific inhibitor of NOX, which in turn effectively inhibited wound-healing and increased susceptibility to microbial infection and decay in 1-month-old tubers. Wound-induced superoxide production was also inhibited by EGTA-mediated destabilization of membranes. The ability to restore superoxide production to EGTA-treated tissue with Ca(+2) declined with advancing tuber age, likely a consequence of age-related changes in membrane architecture. Of the five homologues of NOX (Strboh A-D and F), wounding induced the expression of Strboh A in 6-month-old tubers but this response was absent in tubers stored for 25-30 months. Strboh A thus mediates the initial burst of superoxide in response to wounding of potato tubers; loss of its expression increases the susceptibility to microbial infection and contributes to the age-induced loss of wound-healing ability.

show abstract

“…In each of the four genetic subgroups of CGD, transfer of a correct copy of the altered gene into hematopoietic stem cells should correct the defect in respiratory burst oxidase and cure the disease. Although female CGD carriers with a few as 10% oxidase‐positive neutrophils can exhibit few or no symptoms, and although several reports in vitro and in animal models have shown that retroviral‐mediated transfer of gp91 (phox) to CGD bone marrow can reconstitute NADPH oxidase activity and increase resistance to various pathogens (32, 33), human phase I clinical studies in CGD patients have not shown the production of clinically beneficial numbers of corrected neutrophils for extended periods of time (34, 35). These observations, along with the danger of using a high MOI to improve gene transfer rates, suggests that the co‐expression of a linked selectable marker or drug resistance gene that allows for a positive selection of transduced cells could help overcome inefficient gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Gamma‐glutamylcysteine synthetase‐based selection strategy for gene therapy of chronic granulomatous disease and graft‐vs.‐host disease

Rappa

Anzanello

Alexeyev

et al. 2007

European J of Haematology

View full text Add to dashboard Cite

Efficient ex vivo/in vivo selection of genetically modified hematopoietic stem/progenitor cells (HPCs) and T lymphocytes could greatly improve several gene therapy strategies. We have previously reported that primary murine HPCs, transduced with a bicistronic retroviral vector, co-expressing the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) and eGFP, could be selected by l-buthionine-S,R-sulfoximine (BSO). Upon ex vivo transduction with a low, defined gene dosage and BSO selection, HPCs were able to repopulate the bone marrow of syngeneic myeloablated hosts, showing multi-lineage expression [Hum Gene Ther, 16 (2005), 711]. We now provide 'proof-of-principle' that the same strategy can be applied to the gene therapy of graft-vs.-host disease (GVHD) subsequent to allogeneic bone marrow transplantation (ABMT), and of chromosome X-associated chronic granulomatous disease (CGD). Transfer of the herpes simplex virus-thymidine kinase (HSV-Tk) 'suicide' gene into donor T lymphocytes is a potential method to control GVHD after ABMT. However, an efficient selection system is required to eliminate non-HSV-Tk-expressing T lymphocytes before administration to the patient. We now report that, upon transduction with a retroviral vector, co-expressing gamma-GCSh and eGFP, and subsequent selection by BSO, over 95% human T lymphocytes were found to express eGFP; moreover, upon transduction with a novel retroviral vector co-expressing gamma-GCSh and HSV-Tk, and subsequent BSO treatment, over 95% of T lymphocytes could be eliminated by ganciclovir. The efficacy of the gamma-GCSh-BSO selection strategy was then tested on an in vitro model of CGD. Upon transduction of gp91 (phox)-deficient PLBKO cells with a novel bicistronic retroviral vector co-expressing human gp91 (phox) and gamma-GCSh, exposure to BSO for 48 h eliminated most non-transduced cells, resulting in selection of gp91 (phox)-expressing cells, and reconstitution of NADPH oxidase activity.

show abstract

Reconstitution of NADPH Oxidase Activity in Human X-Linked Chronic Granulomatous Disease Myeloid Cells after Stable Gene Transfer Using a Recombinant Adeno- Associated Virus 2 Vector

Cited by 9 publications

References 62 publications

Lentivirus-mediated gene transfer of gp91phox corrects chronic granulomatous disease (CGD) phenotype in human X-CGD cells

Lentivirus-mediated gene transfer of gp91phox corrects chronic granulomatous disease (CGD) phenotype in human X-CGD cells

Strboh A homologue of NADPH oxidase regulates wound-induced oxidative burst and facilitates wound-healing in potato tubers

Gamma‐glutamylcysteine synthetase‐based selection strategy for gene therapy of chronic granulomatous disease and graft‐vs.‐host disease

Contact Info

Product

Resources

About