| Title |
Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells
|
|---|---|
| Published in |
International Journal of Nanomedicine, March 2017
|
| DOI | 10.2147/ijn.s128611 |
| Pubmed ID | |
| Authors |
Julie Brault, Guillaume Vaganay, Aline Le Roy, Jean-Luc Lenormand, Sandra Cortes, Marie José Stasia |
| Abstract |
Chronic 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 X(0)-linked CGD (X(0)-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 X(0)-CGD-induced pluripotent stem cell (iPSC)-derived macrophages. In addition, NADPH oxidase activity was restored in X(0)-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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 35 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 11% |
| Student > Bachelor | 4 | 11% |
| Researcher | 4 | 11% |
| Student > Doctoral Student | 3 | 9% |
| Student > Master | 3 | 9% |
| Other | 5 | 14% |
| Unknown | 12 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 14% |
| Biochemistry, Genetics and Molecular Biology | 5 | 14% |
| Agricultural and Biological Sciences | 4 | 11% |
| Immunology and Microbiology | 4 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Other | 0 | 0% |
| Unknown | 15 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 32. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 February 2022.
All research outputs
#1,220,949
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#40
of 4,122 outputs
Outputs of similar age
#24,469
of 324,443 outputs
Outputs of similar age from International Journal of Nanomedicine
#4
of 95 outputs
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So far Altmetric has tracked 4,122 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done particularly well, scoring higher than 99% of its peers.
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