scholarly journals Bioengineering Strategies for Protein-Based Nanoparticles

Genes ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 370 ◽  
Author(s):  
Dennis Diaz ◽  
Andrew Care ◽  
Anwar Sunna
Keyword(s):  
Drug Delivery ◽  
Vaccine Development ◽  
De Novo ◽  
Practical Application ◽  
Intrinsic Properties ◽  
Protein Assemblies ◽  
Protein Subunits ◽  
Multiple Protein ◽  
Perfect Symmetry ◽  
Genetic Strategies

In recent years, the practical application of protein-based nanoparticles (PNPs) has expanded rapidly into areas like drug delivery, vaccine development, and biocatalysis. PNPs possess unique features that make them attractive as potential platforms for a variety of nanobiotechnological applications. They self-assemble from multiple protein subunits into hollow monodisperse structures; they are highly stable, biocompatible, and biodegradable; and their external components and encapsulation properties can be readily manipulated by chemical or genetic strategies. Moreover, their complex and perfect symmetry have motivated researchers to mimic their properties in order to create de novo protein assemblies. This review focuses on recent advances in the bioengineering and bioconjugation of PNPs and the implementation of synthetic biology concepts to exploit and enhance PNP’s intrinsic properties and to impart them with novel functionalities.

Artificial protein assemblies with well-defined supramolecular protein nanostructures

2021 ◽  
Author(s):  
Suyeong Han ◽  
Yongwon Jung
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
Building Blocks ◽  
Protein Assembly ◽  
Protein Assemblies ◽  
Cellular Processes ◽  
Wide Range ◽  
Array Structures ◽  
Small Chemical ◽  
Artificial Protein

Nature uses a wide range of well-defined biomolecular assemblies in diverse cellular processes, where proteins are major building blocks for these supramolecular assemblies. Inspired by their natural counterparts, artificial protein-based assemblies have attracted strong interest as new bio-nanostructures, and strategies to construct ordered protein assemblies have been rapidly expanding. In this review, we provide an overview of very recent studies in the field of artificial protein assemblies, with the particular aim of introducing major assembly methods and unique features of these assemblies. Computational de novo designs were used to build various assemblies with artificial protein building blocks, which are unrelated to natural proteins. Small chemical ligands and metal ions have also been extensively used for strong and bio-orthogonal protein linking. Here, in addition to protein assemblies with well-defined sizes, protein oligomeric and array structures with rather undefined sizes (but with definite repeat protein assembly units) also will be discussed in the context of well-defined protein nanostructures. Lastly, we will introduce multiple examples showing how protein assemblies can be effectively used in various fields such as therapeutics and vaccine development. We believe that structures and functions of artificial protein assemblies will be continuously evolved, particularly according to specific application goals.

Chitosan Nanoparticles: An Approbative System for the Delivery of Herbal Bioactives

2020 ◽  
Vol 10 ◽  
Author(s):  
Sapna Saini ◽  
Sanju Nanda ◽  
Anju Dhiman
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
State Of The Art ◽  
Chitosan Nanoparticles ◽  
Delivery Systems ◽  
Intrinsic Properties ◽  
Amino Groups ◽  
Suitable Candidate ◽  
Film Forming ◽  
Novel Drug

: Chitosan, a natural biodegradable polymer obtained from deacetylation of chitin, has been used as an approbative macromolecule for the development of various novel drug delivery systems. It is one of the most favorable biodegradable carriers for nanoparticulate drug delivery due to its intrinsic properties, such as biocompatibility, biodegradability, non-toxicity, availability of free reactive amino groups, and ease of chemical modification into different active derivatives. Furthermore, interesting physical properties (film-forming, gelling and thickening) make it a suitable candidate for formulations, such as films, microcapsules, beads, nanoparticles, nanofibres, nanogel and so on. Researchers have reported that chitosan nanoparticles act as a promising vehicle for herbal actives as they provide a superior alternative to traditional carriers and improve pharmaceutical efficiency. As no review of chitosan nanoparticles encapsulating herbal extracts and bioactives has been published till date, a maiden effort has been made to collate and review the use of chitosan nanoparticles for the entrapment of phytoconstituents to yield stable, efficient and safe drug delivery systems. Additionally, the paper presents a comprehensive account of the state-of the-art in fabricating herbal chitosan nanoparticles and their current pharmacological status. A list of patents on chitosan nanoparticles of herbal actives has also been included. This review is intended to serve as a didactic discourse for the formulation scientists endeavoring to develop advanced delivery systems for herbal actives.

scholarly journals Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1078 ◽  
Author(s):  
Albert Ros-Lucas ◽  
Florencia Correa-Fiz ◽  
Laia Bosch-Camós ◽  
Fernando Rodriguez ◽  
Julio Alonso-Padilla
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
De Novo ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Economic Losses ◽  
Virus Protein ◽  
Hemorrhagic Disease ◽  
Starting Point

African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4+ T-cell and 6 CD8+ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

scholarly journals Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fengbin Wang ◽  
Ordy Gnewou ◽  
Charles Modlin ◽  
Leticia C. Beltran ◽  
Chunfu Xu ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Synthetic Peptide ◽  
Quaternary Structure ◽  
De Novo ◽  
Rational Approach ◽  
Lateral Interactions ◽  
Protein Assemblies ◽  
Self Assembling ◽  
Arginine Residues ◽  
Insight Into

AbstractThe exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili.

scholarly journals Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cui Zhang ◽  
Cihan Oguz ◽  
Sue Huse ◽  
Lu Xia ◽  
Jian Wu ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Malaria Parasite ◽  
Vaccine Development ◽  
De Novo ◽  
Gene Families ◽  
Plasmodium Yoelii ◽  
Control Measures ◽  
Effective Control ◽  
Malaria Parasites ◽  
Rodent Malaria

Abstract Background Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated. Results We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains. Conclusions The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.

scholarly journals Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes

2006 ◽  
Vol 14 (2) ◽  
pp. 182-189 ◽  
Author(s):  
David H. Holman ◽  
Danher Wang ◽  
Kanakatte Raviprakash ◽  
Nicholas U. Raja ◽  
Min Luo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Vaccine Development ◽  
De Novo ◽  
Natural Infection ◽  
Hemorrhagic Fever ◽  
Virus Infections ◽  
Dengue Vaccine ◽  
Membrane Antigens ◽  
Dengue Virus Serotypes

ABSTRACT Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

scholarly journals In silico identification of vaccine targets for 2019-nCoV

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 145 ◽  
Author(s):  
Chloe Hyun-Jung Lee ◽  
Hashem Koohy
Keyword(s):  
T Cell ◽  
In Silico ◽  
Vaccine Development ◽  
De Novo ◽  
Cell Receptor ◽  
Binding Potential ◽  
Hla Alleles ◽  
Immunogenic Peptides ◽  
Novel Coronavirus ◽  
Positional Weight

Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.

scholarly journals Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

2020 ◽  
Author(s):  
Nicholas C Palmateer ◽  
Kyle Tretina ◽  
Joshua Orvis ◽  
Olukemi O Ifeonu ◽  
Jonathan Crabtree ◽  
...  
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
High Specificity ◽  
Theileria Parva ◽  
Nucleotide Polymorphisms ◽  
Specificity And Sensitivity ◽  
Genome Wide ◽  
Dna Capture ◽  
High Level ◽  
Genome Assemblies

AbstractTheileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ∼54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is larger than the genome from the reference, cattle-derived, Muguga strain. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average FST, genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species, with clear implications for vaccine development. The DNA capture approach used provides clear advantages over alternative T. parva DNA enrichment methods used previously and enables in-depth comparative genomics in this apicomplexan parasite.

scholarly journals Characterization of a New γTuRC Subunit with WD Repeats

2003 ◽  
Vol 14 (3) ◽  
pp. 1017-1026 ◽  
Author(s):  
Ruwanthi N. Gunawardane ◽  
Ona C. Martin ◽  
Yixian Zheng
Keyword(s):  
Microtubule Assembly ◽  
Guanine Nucleotide ◽  
Protein Subunits ◽  
Multiple Protein ◽  
Tubulin Binding ◽  
Ring Complex ◽  
Signature Sequences ◽  
Complete Set ◽  
Wd Repeats

The γ-tubulin ring complex (γTuRC), consisting of multiple protein subunits, can nucleate microtubule assembly. Although many subunits of the γTuRC have been identified, a complete set remains to be defined in any organism. In addition, how the subunits interact with each other to assemble into γTuRC remains largely unknown. Here, we report the characterization of a novel γTuRC subunit, Drosophila gamma ring protein with WD repeats (Dgp71WD). With the exception of γ-tubulin, Dgp71WD is the only γTuRC component identified to date that does not contain the grip motifs, which are signature sequences conserved in γTuRC components. By performing immunoprecipitations after pair-wise coexpression in Sf9 cells, we show that Dgp71WD directly interacts with the grip motif–containing γTuRC subunits, Dgrips84, 91, 128, and 163, suggesting that Dgp71WD may play a scaffolding role in γTuRC organization. We also show that Dgrips128 and 163, like Dgrips84 and 91, can interact directly with γ-tubulin. Coexpression of any of these grip motif–containing proteins with γ-tubulin promotes γ-tubulin binding to guanine nucleotide. In contrast, in the same assay Dgp71WD interacts with γ-tubulin but does not facilitate nucleotide binding.

scholarly journals COVID-19: Current Developments and Further Opportunities in Drug Delivery and Therapeutics

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 945
Author(s):  
Saman Zafar ◽  
Muhammad Sohail Arshad ◽  
Sameen Fatima ◽  
Amna Ali ◽  
Aliyah Zaman ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Vaccine Development ◽  
Viral Vector ◽  
Age Groups ◽  
World Health ◽  
Disease Spread ◽  
Plasma Therapy ◽  
Antiviral Therapies ◽  
Health Organization ◽  
Spread Of Infection

SARS-CoV-2 has affected people from all age groups, races and ethnicities. Given that many infected individuals are asymptomatic, they transmit the disease to others unknowingly, which has resulted in the spread of infection at an alarming rate. This review aims to provide an overview of the pathophysiology, preventive measures to reduce the disease spread, therapies currently in use, an update on vaccine development and opportunities for vaccine delivery. The World Health Organization has advised several precautions including social distancing, hand washing and the use of PPE including gloves and face masks for minimizing the spread of SARS-CoV-2 infection. At present, several antiviral therapies previously approved for other infections are being repositioned to study their efficacy against SARS-CoV-2. In addition, some medicines (i.e., remdesivir, chloroquine, hydroxychloroquine) have received emergency use authorisation from the FDA. Plasma therapy has also been authorised for emergency use for the treatment of COVID-19 on a smaller scale. However, no vaccine has been approved so far against this virus. Nevertheless, several potential vaccine targets have been reported, and development of different types of vaccines including DNA, mRNA, viral vector, inactivated, subunit and vaccine-like particles is in process. It is concluded that a suitable candidate delivered through an advanced drug delivery approach would effectively boost the immune system against this coronavirus.

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