Development of a Multifunctional Nanobiointerface Based on Self-Assembled Fusion-Protein rSbpA/ZZ for Blood Cell Enrichment and Phenotyping

2017 ◽  
Vol 9 (39) ◽  
pp. 34423-34434 ◽  
Author(s):  
Mario Rothbauer ◽  
Martin Frauenlob ◽  
Karoline Gutkas ◽  
Michael B. Fischer ◽  
Eva-Kathrin Sinner ◽  
...  
Keyword(s):  
Blood Cell ◽  
Fusion Protein ◽  
Cell Enrichment ◽  
Self Assembled

Cell-Permeable, MMP-2 Activatable, Nickel Ferrite and His-Tagged Fusion Protein Self-Assembled Fluorescent Nanoprobe for Tumor Magnetic-Targeting and Imaging

2017 ◽  
Vol 9 (45) ◽  
pp. 39209-39222 ◽  
Author(s):  
Lu Sun ◽  
Shuping Xie ◽  
Jing Qi ◽  
Ergang Liu ◽  
Di Liu ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Nickel Ferrite ◽  
Magnetic Targeting ◽  
Fluorescent Nanoprobe ◽  
Self Assembled

scholarly journals Rational engineering of an erythropoietin fusion protein to treat hypoxia

2021 ◽  
Author(s):  
Jungmin Lee ◽  
Andyna Vernet ◽  
Nathalie G. Gruber ◽  
Kasia M. Kready ◽  
Devin R. Burrill ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Blood Cell ◽  
Fusion Protein ◽  
Red Blood Cell ◽  
Receptor Activation ◽  
Erythropoietin Receptor ◽  
Neuroprotective Activity ◽  
Erythroid Cell ◽  
Glycophorin A

Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10-14M, allowing an estimate of the number of receptor-ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.

RAP-011, a Soluble Activin Receptor Type IIa Murine IgG-Fc Fusion Protein, Prevents Chemotherapy Induced Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 161-161 ◽  
Author(s):  
Aaron W Mulivor ◽  
Denise Barbosa ◽  
Ravi Kumar ◽  
Matthew Leigh Sherman ◽  
Jas Seehra ◽  
...  
Keyword(s):  
Blood Cell ◽  
Fusion Protein ◽  
Treated Group ◽  
Receptor Type ◽  
Severe Side Effect ◽  
Recombinant Erythropoietin ◽  
Activin Receptor ◽  
Treatment Regimens ◽  
Cell Counts ◽  
Increased Risk

Abstract Abstract 161 Anemia is a common and often severe side-effect of chemotherapy treatment that can alter treatment regimens and can frequently require patients to receive blood transfusions. The majority of therapies approved for anemia target the erythropoietin (EPO) pathway. However, recent studies suggest an increased risk of mortality associated with recombinant erythropoietin (EPO) and its derivatives, which may stimulate tumor progression and increase the occurrence of thromboembolic events. The TGF-β superfamily of proteins has been reported to play a role in red blood cell (RBC) development, but works via a different pathway from EPO. RAP-011 is a murine fusion protein based on the activin receptor type IIA (ActRIIA) that binds to and prevents signaling of certain members of the TGF-β superfamily through the ActRIIA receptor. The purpose of the current study is to evaluate the effect of RAP-011 on chemotherapy induced anemia (CIA) in a mouse model. To investigate the ability of RAP-011 to prevent anemia, six week old C57BL/6 mice (30/dose group) were treated with Vehicle (VEH), or RAP-011 (1 mg/kg, 10 mg/kg, 30 mg/kg) 7 days prior to chemotherapy (Day -7). On Day 0, the mice received a single dose of paclitaxel (25 mg/kg) to induce CIA. 10 mice from each treatment group were sacrificed on Days 0, 3 and 7 and blood was collected for complete blood cell counts. On study day 0, immediately prior to CIA induction, VEH treated mice had an average hematocrit of 41.6% and RAP-011 treated mice had significantly increased hematocrits compared to the VEH cohort (1 mg/kg 43.4%, P<0.001; 10 mg/kg 42.7%, P<0.001; 30 mg/kg 43.59%, P<0.001). Similarly, VEH treated mice had an average hemoglobin level of 154.4 g/l and RAP-011 treated mice had significantly increased levels compared to the VEH cohort (1 mg/kg 167.2 g/l, P<0.001; 10 mg/kg 167.1 g/l, P<0.001; 30 mg/kg 170.1 g/l, P<0.001). 3 days following CIA the hematocrit in VEH treated mice was decreased to 38.3%. The hematocrit in RAP-011 treated groups decreased as well, but was significantly greater than VEH controls (1 mg/kg 41.0%, P<0.001; 10 mg/kg 42.9%, P<0.001; 30 mg/kg 42.3%, P<0.001). Hemoglobin measurements followed a similar pattern with VEH treated mice being decreased (137.0 g/l) whereas all of the RAP-011 treated cohorts were decreased but were significantly greater than the VEH cohort (1 mg/kg 150.8 g/l, P<0.001; 10 mg/kg 154.3 g/l, P<0.001; 30 mg/kg 151.2 g/l, P<0.001). One week following CIA the hematocrit in VEH treated mice was still decreased compared to the baseline measurements (40.7%, P<0.001). The lowest dose RAP-011 treated group was decreased as well (1 mg/kg 42.9%, P<0.001). However, the higher RAP-011 dosed cohorts had returned to their baseline values and were significantly higher than the VEH treated cohort (10 mg/kg 44.6%, P<0.001; 30 mg/kg 43.8%, P<0.001). Hemoglobin levels in the VEH cohort returned to baseline levels (150.5 g/l) and all of the RAP-011 treated cohorts were significantly increased compared to VEH (1 mg/kg 161.4 g/l, P<0.05; 10 mg/kg 171.7 g/l, P<0.001; 30 mg/kg 167.2 g/l, P<0.001). These data suggest that altering signaling in the TGFβ superfamily by use of a soluble ActRIIA receptor might act as a novel anemia therapy in patients receiving chemotherapy. Towards this end, ACE-011, the human analog of RAP-011, is currently in clinical development for the treatment of chemotherapy induced anemia. Disclosures: Mulivor: Acceleron Pharma: Employment. Barbosa:Acceleron Pharma: Employment. Kumar:Acceleron Pharma: Employment. Sherman:Acceleron: Employment, Equity Ownership. Seehra:Acceleron Pharma: Employment. Pearsall:Acceleron Pharma: Employment.

scholarly journals Self-Assembled Amyloid-Like Oligomeric-Cohesin Scaffoldin for Augmented Protein Display on the Saccharomyces cerevisiae Cell Surface

2012 ◽  
Vol 78 (9) ◽  
pp. 3249-3255 ◽  
Author(s):  
Zhenlin Han ◽  
Bei Zhang ◽  
Yi E. Wang ◽  
Yi Y. Zuo ◽  
Wei Wen Su
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Fusion Protein ◽  
Fold Increase ◽  
Scaffolding Protein ◽  
Yeast Display ◽  
Protein Scaffold ◽  
Content Type ◽  
Self Assembled ◽  
Novel Protein

ABSTRACTIn this study, a molecular self-assembly strategy to develop a novel protein scaffold for amplifying the extent and variety of proteins displayed on the surface ofSaccharomyces cerevisiaeis presented. The cellulosomal scaffolding protein cohesin and its upstream hydrophilic domain (HD) were genetically fused with the yeast Ure2p N-terminal fibrillogenic domain consisting of residues 1 to 80 (Ure2p1-80). The resulting Ure2p1-80-HD-cohesin fusion protein was successfully expressed inEscherichia colito produce self-assembled supramolecular nanofibrils that serve as a novel protein scaffold displaying multiple copies of functional cohesin domains. The amyloid-like property of the nanofibrils was confirmed via thioflavin T staining and atomic force microscopy. These cohesin nanofibrils attached themselves, via a green fluorescent protein (GFP)-dockerin fusion protein, to the cell surface ofS. cerevisiaeengineered to display a GFP-nanobody. The excess cohesin units on the nanofibrils provide ample sites for binding to dockerin fusion proteins, as exemplified using an mCherry-dockerin fusion protein as well as theClostridium cellulolyticumCelA endoglucanase. More than a 24-fold increase in mCherry fluorescence and an 8-fold increase in CelA activity were noted when the cohesin nanofibril scaffold-mediated yeast display was used, compared to using yeast display with GFP-cohesin that contains only a single copy of cohesin. Self-assembled supramolecular cohesin nanofibrils created by fusion with the yeast Ure2p fibrillogenic domain provide a versatile protein scaffold that expands the utility of yeast cell surface display.

scholarly journals Enhanced Neutralization Potency of Botulinum Neurotoxin Antibodies Using a Red Blood Cell-Targeting Fusion Protein

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17491 ◽  
Author(s):  
Sharad P. Adekar ◽  
Andrew T. Segan ◽  
Cindy Chen ◽  
Rodney Bermudez ◽  
M. D. Elias ◽  
...  
Keyword(s):  
Blood Cell ◽  
Fusion Protein ◽  
Red Blood Cell ◽  
Botulinum Neurotoxin ◽  
Cell Targeting

High-throughput residual white blood cell counter enabled by microfluidic cell enrichment and reagent-containing patch integration

2019 ◽  
Vol 283 ◽  
pp. 549-555 ◽  
Author(s):  
Byeongyeon Kim ◽  
Suyeon Shin ◽  
Yujin Lee ◽  
Changyong Um ◽  
Dongwon You ◽  
...  
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
High Throughput ◽  
Cell Enrichment ◽  
Cell Counter

Self-assembled adhesive biomaterials formed by a genetically designed fusion protein

2018 ◽  
Vol 54 (89) ◽  
pp. 12642-12645 ◽  
Author(s):  
Pulakesh Aich ◽  
Jaeyeon An ◽  
Byeongseon Yang ◽  
Young Ho Ko ◽  
Junghyun Kim ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Adhesion Property ◽  
Underwater Adhesion ◽  
Genetic Fusion ◽  
Self Assembled ◽  
Mussel Foot Protein

A spider with mussel: a supramolecular fiber formed by a spider dragline protein was tuned to have underwater adhesion property by genetic fusion of a mussel foot protein.

RAP-536, A Soluble Activin Receptor Type IIb Murine IgG-Fc Fusion Protein, Prevents Myelodysplastic Syndrome Related Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 978-978 ◽  
Author(s):  
Aaron Mulivor ◽  
Samuel M. Cadena ◽  
Rajasekhar NVS Suragani ◽  
Ravindra Kumar ◽  
Kathryn Underwood ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Blood Cell ◽  
Fusion Protein ◽  
Myelodysplastic Syndrome ◽  
Red Blood Cell ◽  
Dose Group ◽  
Cell Mass ◽  
Severe Anemia ◽  
Wild Type ◽  
Leukocyte Counts

Abstract Abstract 978 Myelodysplastic syndrome (MDS) is a premalignant disease characterized by ineffective hematopoiesis. MDS patients can live for extended periods of time but can develop severe anemia or may progress to acute leukemia. Current therapies require patients to receive chemotherapy and/or blood transfusions to either prevent progression to leukemia or improve anemia. The majority of therapies approved for anemia target the erythropoietin (EPO) pathway. However, recent studies suggest an increased risk of mortality associated with recombinant erythropoietin (EPO) and its derivatives, which may stimulate tumor progression and increase the occurrence of thromboembolic events. While Lenalidomide has shown efficacy in reducing red cell transfusion rates, particularly in the del(5q) subset of MDS patients, additional therapies that increase red blood cell mass would be beneficial. Proteins in the TGF-β superfamily have been reported to play a role in red blood cell (RBC) development, but they act via a different pathway from EPO. RAP-536 is a murine soluble receptor fusion protein based on the activin receptor type IIB (ActRIIB) that binds to certain TGF-β ligands and prevents signaling through the ActRIIB receptor. The purpose of the current study is to evaluate the hematopoietic effect of RAP-536 in a mouse model of MDS. To investigate the effects of RAP-536 in a model of MDS, three month old NUP98-HOX13 transgenic mice (10/dose group) were treated with Vehicle (VEH), or RAP-536 (10 mg/kg) twice per week for the duration of the study. Wild-type littermates (10/dose group) were dosed with VEH or RAP-536 (10 mg/kg) and used as controls. Blood samples and blood smears were collected monthly to conduct CBC measurements and assess changes in blood cells. On study day 0, immediately prior to the first dosing, the NUP98-HOX13 transgenic male mice had significantly decreased levels of RBC (-8.8%, P<0.05), hematocrit (-8.4%, P<0.05) and leukocytes (-67.6%, P<0.001) compared to their wild-type control littermates. Similar trends were seen in female NUP98-HOX13 transgenic mice with RBC (-1.1%) and hematocrit (-2.2%) decreased but not significantly and leukocytes (-68%, P<0.01) decreased significantly compared to the wild type controls. After 1 month of dosing, male NUP98-HOX13 transgenic mice treated with RAP-536 had significantly increased RBC counts (+9.2%, P<0.01), hemoglobin (+13.1%, P<0.01) and hematocrit (+10.8%, P<0.01) compared to their VEH controls. Female NUP98-HOX13 transgenic mice treated with RAP-536 had significant increases in RBC (+3.0%, P<0.05) and hematocrit (+4.9%, P<0.05) when compared to VEH controls. There were no significant changes in leukocyte counts between RAP-536 and VEH treated NUP98-HOX13 transgenic mice in either the male or female cohorts. RAP-536 treatment also had no effect on leukocyte number in wild-type mice. It should be noted that all of the transgenic mice had lower leukocyte counts compared to their wild-type littermates. After 4 months of dosing, NUP98-HOX13 transgenic mice treated with RAP-536 had increased RBC counts (+25.4%, P<0.01), hemoglobin (+22.8%, P<0.01) and hematocrit (+21.9%, P<0.01) in males as well as females (+16.2%, P<0.05; +16.9%, P<0.01; +18.4%, P<0.01) compared to VEH treated controls. All transgenic mice continued to have lower leukocyte counts compared to wild type controls, but there were no significant changes in leukocyte counts between RAP-536 and VEH treated NUP98-HOX13 transgenic mice in either the male or female cohorts. These data suggest that the use of a modified soluble ActRIIB receptor acts to increase red blood cell mass and represents a novel therapy for severe anemia in patients with Myelodysplastic syndrome and other hematopoietic diseases. Disclosures: Mulivor: Acceleron Pharma: Employment. Cadena:Acceleron Pharma: Employment. Suragani:Acceleron Pharma: Employment. Kumar: Acceleron Pharma: Employment. Underwood:Acceleron Pharma: Employment. Seehra: Acceleron Pharma: Employment. Pearsall:Acceleron Pharma: Employment.

scholarly journals A self-assembled fusion protein-based surface plasmon resonance biosensor for rapid diagnosis of severe acute respiratory syndrome

Talanta ◽  
2009 ◽  
Vol 79 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Tae Jung Park ◽  
Moon Seop Hyun ◽  
Hye Jin Lee ◽  
Sang Yup Lee ◽  
Sungho Ko
Keyword(s):  
Surface Plasmon Resonance ◽  
Severe Acute Respiratory Syndrome ◽  
Fusion Protein ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Rapid Diagnosis ◽  
Surface Plasmon Resonance Biosensor ◽  
Self Assembled

Poly(ɛ-caprolactone) modified with fusion protein containing self-assembled hydrophobin and functional peptide for selective capture of human blood outgrowth endothelial cells

2013 ◽  
Vol 101 ◽  
pp. 361-369 ◽  
Author(s):  
Yujian Huang ◽  
Suai Zhang ◽  
Baolong Niu ◽  
Dandan Wang ◽  
Zefang Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fusion Protein ◽  
Human Blood ◽  
Self Assembled ◽  
Functional Peptide
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