scholarly journals Pre-clinical optimisation and safety studies of a new lentiviral gene therapy for p47phox-deficient chronic granulomatous disease

2021 ◽  
Author(s):  
Andrea Schejtman ◽  
Winston Vetharoy ◽  
Uimook Choi ◽  
Christine Rivat ◽  
Narda Theobald ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Safety Studies ◽  
Lentiviral Gene Therapy

scholarly journals Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease

PEDIATRICS ◽  
2020 ◽  
Vol 146 (Supplement 4) ◽  
pp. S380.2-S381
Author(s):  
Mamatha Mandava ◽  
Kelli W. Williams
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Lentiviral Gene Therapy

scholarly journals Non-Clinical Efficacy and Safety Studies on G1XCGD, a Lentiviral Vector for Ex Vivo Gene Therapy of X-Linked Chronic Granulomatous Disease

2018 ◽  
Vol 29 (2) ◽  
pp. 69-79 ◽  
Author(s):  
Christian Brendel ◽  
Michael Rothe ◽  
Giorgia Santilli ◽  
Sabine Charrier ◽  
Stefan Stein ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Clinical Efficacy ◽  
Lentiviral Vector ◽  
Ex Vivo ◽  
Granulomatous Disease ◽  
Efficacy And Safety ◽  
Safety Studies ◽  
Ex Vivo Gene Therapy

scholarly journals Lentiviral gene therapy for X-linked chronic granulomatous disease

2020 ◽  
Vol 26 (2) ◽  
pp. 200-206 ◽  
Author(s):  
Donald B. Kohn ◽  
◽  
Claire Booth ◽  
Elizabeth M. Kang ◽  
Sung-Yun Pai ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Lentiviral Gene Therapy

scholarly journals Lentiviral gene therapy rescues p47phox chronic granulomatous disease and the ability to fight Salmonella infection in mice

Gene Therapy ◽  
2020 ◽  
Vol 27 (9) ◽  
pp. 459-469 ◽  
Author(s):  
Andrea Schejtman ◽  
Walmir Cutrim Aragão-Filho ◽  
Simon Clare ◽  
Marta Zinicola ◽  
Maren Weisser ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Bacterial Load ◽  
Cathepsin G ◽  
Granulomatous Disease ◽  
Hematopoietic Stem ◽  
Therapy Approach ◽  
Gene Therapy Approach ◽  
Lentiviral Gene Therapy

Abstract Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder characterised by recurrent and often life-threatening infections and hyperinflammation. It is caused by defects of the phagocytic NADPH oxidase, a multicomponent enzyme system responsible for effective pathogen killing. A phase I/II clinical trial of lentiviral gene therapy is underway for the most common form of CGD, X-linked, caused by mutations in the gp91phox subunit of the NADPH oxidase. We propose to use a similar strategy to tackle p47phox-deficient CGD, caused by mutations in NCF1, which encodes the p47phox cytosolic component of the enzymatic complex. We generated a pCCLCHIM-p47phox lentiviral vector, containing the chimeric Cathepsin G/FES myeloid promoter and a codon-optimised version of the human NCF1 cDNA. Here we show that transduction with the pCCLCHIM-p47phox vector efficiently restores p47phox expression and biochemical NADPH oxidase function in p47phox-deficient human and murine cells. We also tested the ability of our gene therapy approach to control infection by challenging p47phox-null mice with Salmonella Typhimurium, a leading cause of sepsis in CGD patients, and found that mice reconstituted with lentivirus-transduced hematopoietic stem cells had a reduced bacterial load compared with untreated mice. Overall, our results potentially support the clinical development of a gene therapy approach using the pCCLCHIM-p47phox vector.

scholarly journals CD34+ peripheral blood progenitors as a target for genetic correction of the two flavocytochrome b558 defective forms of chronic granulomatous disease

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 53-58 ◽  
Author(s):  
F Li ◽  
GF Linton ◽  
S Sekhsaria ◽  
N Whiting-Theobald ◽  
JP Katkin ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Leukemia Virus ◽  
Single Gene ◽  
Fold Increase ◽  
Granulomatous Disease ◽  
Flavocytochrome B558 ◽  
O2 Production

Abstract Chronic granulomatous disease (CGD) can result from any of four single gene defects involving components of the superoxide (O2-.)-generating phagocyte NADPH oxidase (phox). The phox transmembrane flavocytochrome b558 is composed of two peptides, gp91phox and p22phox. Mutations of gp91phox cause X-linked CGD, whereas mutations of p22phox cause one of the three autosomal recessive forms of CGD. We used the Maloney leukemia virus-based MFG retrovirus vector to produce replication defective retroviruses encoding gp91phox or p22phox. To maximize viral titer MFG retroviruses do not contain internal promoter or resistance elements. Epstein-Barr virus transformed B-lymphocyte cell lines (EBV- B) derived from normal individuals contain phox components and produce O2-., whereas those derived from CGD patients show the CGD defect. Transduction of gp91phox or p22phox-deficient CGD EBV-B lines resulted in correction of O2-. production from a barely detectable baseline to an average 7.2% and 13.8% of normal control, respectively, without any selective regimen to enrich for transduced cells. CD34+ hematopoietic progenitor cells, the therapeutic target for gene therapy of CGD, were isolated from peripheral blood of CGD patients, transduced with MFG- phox retroviruses, and differentiated in culture to mature phagocytes. Transduction of progenitors corrected the gp91phox (seven patients) and p22phox (two patients) CGD phagocyte oxidase defect to 2.5% and 4.9% of normal O2-. production, respectively, representing an 87-fold and 161- fold increase. These studies show correction of flavocytochrome b558- deficient CGD in primary hematopoietic progenitors, providing a basis for development of gene therapy for the X-linked gp91phox and autosomal p22phox-deficient forms of CGD.

Gene therapy for chronic granulomatous disease

1998 ◽  
Vol 35 (11-12) ◽  
pp. 695-696
Author(s):  
A THRASHER
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease

scholarly journals From Bench to Bedside: Preclinical Evaluation of a Self-Inactivating Gammaretroviral Vector for the Gene Therapy of X-linked Chronic Granulomatous Disease

2013 ◽  
Vol 24 (2) ◽  
pp. 86-98 ◽  
Author(s):  
Stefan Stein ◽  
Simone Scholz ◽  
Joachim Schwäble ◽  
Mohammed A. Sadat ◽  
Ute Modlich ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Preclinical Evaluation

Gene therapy for chronic granulomatous disease

2007 ◽  
Vol 7 (12) ◽  
pp. 1799-1809 ◽  
Author(s):  
Martin F Ryser ◽  
Joachim Roesler ◽  
Marcus Gentsch ◽  
Sebastian Brenner
Keyword(s):  
Gene Therapy ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease
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