scholarly journals Delivery of mRNA Vaccine against SARS-CoV-2 Using a Polyglucin:Spermidine Conjugate

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 76
Author(s):  
Larisa I. Karpenko ◽  
Andrey P. Rudometov ◽  
Sergei V. Sharabrin ◽  
Dmitry N. Shcherbakov ◽  
Mariya B. Borgoyakova ◽  
...  

One of the key stages in the development of mRNA vaccines is their delivery. Along with liposome, other materials are being developed for mRNA delivery that can ensure both the safety and effectiveness of the vaccine, and also facilitate its storage and transportation. In this study, we investigated the polyglucin:spermidine conjugate as a carrier of an mRNA-RBD vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The conditions for the self-assembling of mRNA-PGS complexes were optimized, including the selection of the mRNA:PGS charge ratios. Using dynamic and electrophoretic light scattering it was shown that the most monodisperse suspension of nanoparticles was formed at the mRNA:PGS charge ratio equal to 1:5. The average hydrodynamic particles diameter was determined, and it was confirmed by electron microscopy. The evaluation of the zeta potential of the investigated complexes showed that the particles surface charge was close to the zero point. This may indicate that the positively charged PGS conjugate has completely packed the negatively charged mRNA molecules. It has been shown that the packaging of mRNA-RBD into the PGS envelope leads to increased production of specific antibodies with virus-neutralizing activity in immunized BALB/c mice. Our results showed that the proposed polycationic polyglucin:spermidine conjugate can be considered a promising and safe means to the delivery of mRNA vaccines, in particular mRNA vaccines against SARS-CoV-2.

2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.


2003 ◽  
Vol 68 (9) ◽  
pp. 1647-1662 ◽  
Author(s):  
Valeria Amendola ◽  
Massimo Boiocchi ◽  
Yuri Diaz Fernandez ◽  
Carlo Mangano ◽  
Piersandro Pallavicini

The bis-bidentate ligand R,S-1,2-diphenyl-N,N'-bis(2-quinolinemethylidene)ethane-1,2-diamine (ligand 4), containing two (iminomethyl)quinoline moieties separated by a cis-1,2-diphenylethylene spacer, forms stable complexes with both CuI and CuII. With CuII, the monomeric 1:1 complex [CuII(4)]2+ is obtained both in CH3CN and CH2Cl2. With CuI and overall 1:1 metal/ligand molar ratio, an equilibrium mixture is obtained in CH3CN, consisting of [CuI(4)2]+, [CuI2(4)2]2+ and [CuI2(4)(CH3CN)4]2+. The preponderant species is the two-metal one-ligand "open" complex [CuI2(4)(CH3CN)4]2+, in which each Cu+ cation is coordinated in a tetrahedral fashion by one (iminomethyl)quinoline unit and by two CH3CN molecules. Precipitation from the equilibrium mixture yields only crystals of [CuI2(4)(CH3CN)4](ClO4)2·2CH3CN, whose crystal and molecular structures have been determined. On the other hand, in the poorly coordinating CH2Cl2 solvent, only the dimeric helical [CuI2(4)2]2+ complex is obtained, when the overall metal/ligand 1:1 molar ratio is chosen. Addition of large quantities of acetonitrile to solutions of [CuI2(4)2]2+ in dichlorometane results in the formation of [CuI2(4)(CH3CN)4]2+, i.e. in the solvent-driven disassembling of the CuI helicate. While electrochemistry in CH3CN is poorly defined due to the presence of more than one CuI species, cyclic voltammetry experiments carried out in CH2Cl2 revealed a well defined behavior, with irreversible oxidation of [CuI2(4)2]2+ and irreversible reduction of [CuII(4)]2+ taking place at separate potentials (∆E ≈ 700 mV). Irreversibility and separation of the redox events are due to the self-assembling and disassembling processes following the reduction and oxidation, respectively.


Soft Matter ◽  
2020 ◽  
Vol 16 (28) ◽  
pp. 6599-6607 ◽  
Author(s):  
Pijush Singh ◽  
Souvik Misra ◽  
Nayim Sepay ◽  
Sanjoy Mondal ◽  
Debes Ray ◽  
...  

The self-assembly and photophysical properties of 4-nitrophenylalanine (4NP) are changed with the alteration of solvent and final self-assembly state of 4NP in competitive solvent mixture and are dictated by the solvent ratio.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosanna Puopolo ◽  
Ilaria Sorrentino ◽  
Giovanni Gallo ◽  
Alessandra Piscitelli ◽  
Paola Giardina ◽  
...  

AbstractThe correct immobilization and orientation of enzymes on nanosurfaces is a crucial step either for the realization of biosensors, as well as to guarantee the efficacy of the developed biomaterials. In this work we produced two versions of a chimeric protein, namely ArsC-Vmh2 and Vmh2-ArsC, which combined the self-assembling properties of Vmh2, a hydrophobin from Pleurotus ostreatus, with that of TtArsC, a thermophilic arsenate reductase from Thermus thermophilus; both chimeras were heterologously expressed in Escherichia coli and purified from inclusion bodies. They were characterized for their enzymatic capability to reduce As(V) into As(III), as well as for their immobilization properties on polystyrene and gold in comparison to the native TtArsC. The chimeric proteins immobilized on polystyrene can be reused up to three times and stored for 15 days with 50% of activity loss. Immobilization on gold electrodes showed that both chimeras follow a classic Langmuir isotherm model towards As(III) recognition, with an association constant (KAsIII) between As(III) and the immobilized enzyme, equal to 650 (± 100) L mol−1 for ArsC-Vmh2 and to 1200 (± 300) L mol−1 for Vmh2-ArsC. The results demonstrate that gold-immobilized ArsC-Vmh2 and Vmh2-ArsC can be exploited as electrochemical biosensors to detect As(III).


Leadership ◽  
2021 ◽  
pp. 174271502199649
Author(s):  
Dag Jansson ◽  
Erik Døving ◽  
Beate Elstad

The notion of leadership competencies is a much-debated issue. In this article, we propose that how the leader makes sense of his or her competencies is key to leadership practice. Specifically, we look at how leaders reconcile discrepancies between the self-perceived proficiency of various competencies and their corresponding importance. Empirically, we study leaders within the music domain – how choral conductors make sense of their competencies in the shaping of their professional practice. We investigated how choral leaders in Scandinavia ( N = 638) made sense of their competencies in the face of demands in their working situations. A mixed methodology was used, comprising a quantitative survey with qualitative comments and in-depth interviews with a selection of the respondents. The results show that when choral leaders shape their practice, they frequently face competency gaps that compel them to act or adjust their identity. The key to this sensemaking process is how they move competency elements they master to the foreground and wanting elements to the background. The concept of ‘sensemaking affordance’ is introduced to account for how various leader competency categories are negotiated to safeguard overall efficacy.


Crystals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 678
Author(s):  
Yuqi Han ◽  
Yan Jiang ◽  
Wei Guo ◽  
Bing Li ◽  
Lu Zhang ◽  
...  

Based on the anchoring effect due to the self-assembling behavior of the phospholipid molecules at the interface between the liquid crystal and water phases on the orientation of liquid crystals, the optical response associated with the orientation and structure of liquid crystals with respect to the concentration of 1,2-didodecanoyl-sn-glycero-3-phosphocholine solution has been investigated. The optical response owing to changes in the orientation and structure of the mixed cholesteric liquid crystals with respect to the change in the concentration of phosphatidylcholine has been obtained. Moreover, the feasibility of using as-prepared mixed cholesteric liquid crystals to measure the phosphatidylcholine concentration has been verified. A methodology to measure the reflectance spectrum by using mixed cholesteric liquid crystals to sensitize the phosphatidylcholine concentration has been further realized. The sensitization effect of the mixed cholesteric liquid crystals on the measurement of phosphatidylcholine concentration was also verified.


2021 ◽  
pp. 106807
Author(s):  
Kang Liu ◽  
Xue-Qiang Zha ◽  
Qiang-Ming Li ◽  
Li-Hua Pan ◽  
Jian-Ping Luo

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz4107
Author(s):  
Pei-Pei Yang ◽  
Kuo Zhang ◽  
Ping-Ping He ◽  
Yu Fan ◽  
Xuejiao J. Gao ◽  
...  

Platelets play a critical role in the regulation of coagulation, one of the essential processes in life, attracting great attention. However, mimicking platelets for in vivo artificial coagulation is still a great challenge due to the complexity of the process. Here, we design platelet-like nanoparticles (pNPs) based on self-assembled peptides that initiate coagulation and form clots in blood vessels. The pNPs first bind specifically to a membrane glycoprotein (i.e., CD105) overexpressed on angiogenetic endothelial cells in the tumor site and simultaneously transform into activated platelet-like nanofibers (apNFs) through ligand-receptor interactions. Next, the apNFs expose more binding sites and recruit and activate additional pNPs, forming artificial clots in both phantom and animal models. The pNPs are proven to be safe in mice without systemic coagulation. The self-assembling peptides mimic platelets and achieve artificial coagulation in vivo, thus providing a promising therapeutic strategy for tumors.


2007 ◽  
Vol 32 (2) ◽  
pp. 115-122 ◽  
Author(s):  
Giulia Bonacucina ◽  
Michele Spina ◽  
Monica Misici-Falzi ◽  
Marco Cespi ◽  
Stefania Pucciarelli ◽  
...  

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