An AAVS1-Targeted Minigene Platform for Correction of iPSCs From All Five Types of Chronic Granulomatous Disease

Merling, Randall K.; Sweeney, Colin L.; Chu, Jessica; Bodansky, Aaron; Choi, Uimook; Priel, Debra Long; Kuhns, Douglas B.; Wang, Hongmei; Vasilevsky, Sam; Ravin, Suk See De; Winkler, Thomas; Dunbar, Cynthia E.; Zou, Jizhong; Zarember, Kol A.; Gallin, John I.; Holland, Steven M.; Malech, Harry L.

doi:10.1038/mt.2014.195

Cited by 67 publications

(66 citation statements)

References 30 publications

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“…Additionally, if a patient has a genetic disease-caused hearing loss, an iPS cell-based transplantation therapy would require another crucial step in the repair of the mutation with gene therapy before the iPS cells go back into the patient (Merling et al, 2015).…”

Section: The Role Of Ips Cells As Potential Cures Of Hearing Loss In mentioning

confidence: 99%

“…First of all, safe and dependable iPS cellobtaining methods are not fully developed. Merling et al (2015) obtained iPS cell lines for chronic granulomatous disease (CGD) by peripheral blood CD34+ cell reprogramming and the molecular mutation was repaired by using the zinc finger nuclease technique in cellular lines. Therefore, gene therapy is an available therapeutic option for the correction of genetic mutations in iPS cells of patients with CGD and other immunodeficiencies (Flynn et al, 2015;Merling et al, 2015).…”

Section: Regenerative Medicinementioning

confidence: 99%

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Pluripotent stem cells and their use in hearing loss

Kepekçi¹,

Özturan²,

Köker³

2016

Turk J Biol

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Throughout its half a century of development, stem cell research has included two main fields: embryonic stem (ES) cell research and the reprogramming of body somatic cells. In the present review we focused on stem cell reprogramming and its relation with otolaryngology. The human body somatic cells are transformed into pluripotent cells by three basic methods: the somatic nuclear transfer method, the somatic cell fusion method (getting cellular pluripotent capacity in cellular reprogramming), and by transcription factors influencing the body somatic cells to generate reprogrammed induced pluripotent stem (iPS) cells. ES cells and iPS cells have pluripotency and differentiate into cells originating from the three germ layers; they are preferred for cellular treatment, drug development, and disease modeling research. Because of ethical restrictions in obtaining ES cells, iPS cells are an alternative pluripotent cell source and patient-specific autologous pluripotent cells are obtained by this method. Cellular treatment and regenerative medicine with pluripotent cells are currently developing and we aimed to raise awareness about this topic in our paper on using iPS cell technology in the biological treatment of hearing loss, which is an important area of research in otolaryngology.

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Section: The Role Of Ips Cells As Potential Cures Of Hearing Loss In mentioning

confidence: 99%

Section: Regenerative Medicinementioning

confidence: 99%

Pluripotent stem cells and their use in hearing loss

Kepekçi¹,

Özturan²,

Köker³

2016

Turk J Biol

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“…13 A stage-3 medium is used for HPC expansion, followed by stage 4 medium for neutrophil differentiation. 13,14 Modifications to the procedure are as follows.…”

Section: Neutrophil Differentiation Characterization and Oxidase Fumentioning

confidence: 99%

“…13 A stage-3 medium is used for HPC expansion, followed by stage 4 medium for neutrophil differentiation. 13,14 Modifications to the procedure are as follows. On day 2 of APEL A, media was changed to fresh APEL A, and APEL B culture differentiation was sometimes extended from day 13 to day 18 depending on differentiation progress.…”

Section: Neutrophil Differentiation Characterization and Oxidase Fumentioning

confidence: 99%

Gene-edited pseudogene resurrection corrects p47phox-deficient chronic granulomatous disease

Merling

Kuhns²,

Sweeney

et al. 2016

Blood Advances

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“…19 CGD patient-specific iPSCs were successfully differentiated into neutrophils and/or macrophages recapitulating the ROS-deficient phenotype to test new therapeutic strategies. [20][21][22][23][24][25][26] Then, using confocal microscopy and flow cytometry, we demonstrated the capability of liposomes to transport and deliver recombinant cytochrome b 558 to the membrane of X 0 -linked CGD (X 0 -CGD) iPSC-derived macrophages. Finally, the therapeutic potential of the NOX2/p22 phox liposomes was evidenced by the restoration of the NADPH oxidase activity of these ROS-deficient cells using the nitroblue tetrazolium (NBT) chloride test.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells

Brault¹,

Vaganay²,

Roy³

et al. 2017

IJN

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International audienceChronic granulomatous disease (CGD) is a rare inherited immunodeficiency due to dysfunction of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex leading to severe and recurrent infections in early childhood. The main genetic form is the X-linked CGD leading to the absence of cytochrome b558 composed of NOX2 and p22 phox , the membrane partners of the NADPH oxidase complex. The first cause of death of CGD patients is pulmonary infections. Recombinant proteoliposome-based therapy is an emerging and innovative approach for membrane protein delivery, which could be an alternative local, targeted treatment to fight lung infections in CGD patients. We developed an enzyme therapy using recombinant NOX2/p22 phox liposomes to supply the NADPH oxidase activity in X0-linked CGD (X0-CGD) macrophages. Using an optimized prokaryotic cell-free protein synthesis system, a recombinant cytochrome b558 containing functional hemes was produced and directly inserted into the lipid bilayer of specific liposomes. The size of the NOX2/p22 phox liposomes was estimated to be around 700 nm. These proteoliposomes were able to generate reactive oxygen species (ROS) in an activated reconstituted cell-free NADPH oxidase activation assay in the presence of recombinant p47 phox , p67 phox and Rac, the cytosolic components of the NADPH oxidase complex. Furthermore, using flow cytometry and fluorescence microscopy, we demonstrated that cytochrome b558 was successfully delivered to the plasma membrane of X0-CGD-induced pluripotent stem cell (iPSC)-derived macrophages. In addition, NADPH oxidase activity was restored in X0-CGD iPSC-derived macrophages treated with NOX2/p22 phox liposomes for 8 h without any toxicity. In conclusion, we confirmed that proteoliposomes provide a new promising technology for the delivery of functional proteins to the membrane of targeted cells. This efficient liposomal enzyme replacement therapy will be useful for future treatment of pulmonary infections in CGD patients refractory to conventional anti-infectious treatments

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An AAVS1-Targeted Minigene Platform for Correction of iPSCs From All Five Types of Chronic Granulomatous Disease

Cited by 67 publications

References 30 publications

Pluripotent stem cells and their use in hearing loss

Pluripotent stem cells and their use in hearing loss

Gene-edited pseudogene resurrection corrects p47phox-deficient chronic granulomatous disease

Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells

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