scholarly journals Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nhan H. Nguyen ◽  
Fiona Y. Glassman ◽  
Robert K. Dingman ◽  
Gautam N. Shenoy ◽  
Elizabeth A. Wohlfert ◽  
...  

AbstractThe safety and efficacy of several life-saving therapeutic proteins are compromised due to their immunogenicity. Once a sustained immune response against a protein-based therapy is established, clinical options that are safe and cost-effective become limited. Prevention of immunogenicity of therapeutic proteins prior to their initial use is critical as it is often difficult to reverse an established immune response. Here, we discuss a rational design and testing of a phosphatidylserine-containing nanoparticle platform for novel oral prophylactic reverse vaccination approach, i.e., pre-treatment of a therapeutic protein in the presence of nanoparticles to prevent immunogenicity of protein therapies.

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1437
Author(s):  
Jing Yi Ong ◽  
Andrew Pike ◽  
Ling Ling Tan

The presence of mycotoxins in foodstuffs and feedstuffs is a serious concern for human health. The detection of mycotoxins is therefore necessary as a preventive action to avoid the harmful contamination of foodstuffs and animal feed. In comparison with the considerable expense of treating contaminated foodstuffs, early detection is a cost-effective way to ensure food safety. The high affinity of bio-recognition molecules to mycotoxins has led to the development of affinity columns for sample pre-treatment and the development of biosensors for the quantitative analysis of mycotoxins. Aptamers are a very attractive class of biological receptors that are currently in great demand for the development of new biosensors. In this review, the improvement in the materials and methodology, and the working principles and performance of both conventional and recently developed methods are discussed. The key features and applications of the fundamental recognition elements, such as antibodies and aptamers are addressed. Recent advances in aptasensors that are based on different electrochemical (EC) transducers are reviewed in detail, especially from the perspective of the diagnostic mechanism; in addition, a brief introduction of some commercially available mycotoxin detection kits is provided.


Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 793
Author(s):  
Uroš Zupančič ◽  
Joshua Rainbow ◽  
Pedro Estrela ◽  
Despina Moschou

Printed circuit boards (PCBs) offer a promising platform for the development of electronics-assisted biomedical diagnostic sensors and microsystems. The long-standing industrial basis offers distinctive advantages for cost-effective, reproducible, and easily integrated sample-in-answer-out diagnostic microsystems. Nonetheless, the commercial techniques used in the fabrication of PCBs produce various contaminants potentially degrading severely their stability and repeatability in electrochemical sensing applications. Herein, we analyse for the first time such critical technological considerations, allowing the exploitation of commercial PCB platforms as reliable electrochemical sensing platforms. The presented electrochemical and physical characterisation data reveal clear evidence of both organic and inorganic sensing electrode surface contaminants, which can be removed using various pre-cleaning techniques. We demonstrate that, following such pre-treatment rules, PCB-based electrodes can be reliably fabricated for sensitive electrochemical biosensors. Herein, we demonstrate the applicability of the methodology both for labelled protein (procalcitonin) and label-free nucleic acid (E. coli-specific DNA) biomarker quantification, with observed limits of detection (LoD) of 2 pM and 110 pM, respectively. The proposed optimisation of surface pre-treatment is critical in the development of robust and sensitive PCB-based electrochemical sensors for both clinical and environmental diagnostics and monitoring applications.


Author(s):  
Yongil Yang ◽  
Jun Hyung Lee ◽  
Magen R. Poindexter ◽  
Yuanhua Shao ◽  
Wusheng Liu ◽  
...  

2021 ◽  
Vol 11 (3) ◽  
pp. 253-257
Author(s):  
Arindam Chakraborty ◽  
Dipak Kumar Singha ◽  
Manas Chakraborty ◽  
Payel Mukherjee

Therapeutic protein are one of the prime option of biologicals as per their clinical uses. In recent times, uses of therapeutic protein increases day by day. Protein therapeutics are used extensively to treat various diseases like cancer, AIDS etc. Due to recent advancement in pharmaceutical biotechnology the interest towards therapeutic proteins are augmenting nowadays. Various clinical research are going on in this field to treat different diseases and pharmaceutical industries are also make interest on therapeutic proteins. Among the various treatment options therapeutic protein will provide highest chance of clinical success. Some recent clinical trials demonstrate that therapeutic protein may provide the safe and potential option to treat various diseases, but there are some drawbacks also like some immunogenic issues, safety, stability problem of protein, degradation of protein in various conditions.


2002 ◽  
Vol 45 (10) ◽  
pp. 321-328 ◽  
Author(s):  
H.J. Gijzen

After the discovery of methane gas by Alessandro Volta in 1776, it took about 100 years before anaerobic processes for the treatment of wastewater and sludges were introduced. The development of high rate anaerobic digesters for the treatment of sewage and industrial wastewater took until the nineteen-seventies and for solid waste even till the nineteen-eighties. All digesters have in common that they apply natural anaerobic consortia of microorganisms for degradation and transformation processes. In view of this, it could be rewarding to evaluate the efficiency of natural ecosystems for their possible application. Examples of high rate anaerobic natural systems include the forestomach of ruminants and the hindgut of certain insects, such as termites and cockroaches. These “natural reactors” exhibit volumetric methane production rates as high as 35 l/l.d. The development of anaerobic reactors based on such natural anaerobic systems could produce eco-technologies for the effective management of a wide variety of solid wastes and industrial wastewater. Important limitations of anaerobic treatment of domestic sewage relate to the absence of nutrient and pathogen removal. A combination of anaerobic pre-treatment followed by photosynthetic post-treatment is proposed for the effective recovery of energy and nutrients from sewage. This eco-technology approach is based on the recognition that the main nutrient assimilating capacity is housed in photosynthetic plants. The proposed anaerobic-photosynthetic process is energy efficient, cost effective and applicable under a wide variety of rural and urban conditions. In conclusion: a natural systems approach towards waste management could generate affordable eco-technologies for effective treatment and resource recovery.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pia Gattinger ◽  
Shiva Izadi ◽  
Clemens Grünwald-Gruber ◽  
Somanath Kallolimath ◽  
Alexandra Castilho

The potential therapeutic value of many proteins is ultimately limited by their rapid in vivo clearance. One strategy to limit clearance by metabolism and excretion, and improving the stability of therapeutic proteins, is their fusion to the immunoglobulin fragment crystallizable region (Fc). The Fc region plays multiple roles in (i) dimerization for the formation of “Y”-shaped structure of Ig, (ii) Fc-mediated effector functions, (iii) extension of serum half-life, and (iv) a cost-effective purification tag. Plants and in particular Nicotiana benthamiana have proven to be suitable expression platforms for several recombinant therapeutic proteins. Despite the enormous success of their use for the production of full-length monoclonal antibodies, the expression of Fc-fused therapeutic proteins in plants has shown limitations. Many Fc-fusion proteins expressed in plants show different degrees of instability resulting in high amounts of Fc-derived degradation products. To address this issue, we used erythropoietin (EPO) as a reporter protein and evaluated the efforts to enhance the expression of full-length EPO-Fc targeted to the apoplast of N. benthamiana. Our results show that the instability of the fusion protein is independent from the Fc origin or IgG subclass and from the peptide sequence used to link the two domains. We also show that a similar instability occurs upon the expression of individual heavy chains of monoclonal antibodies and ScFv-Fc that mimic the “Y”-shape of antibodies but lack the light chain. We propose that in this configuration, steric hindrance between the protein domains leads to physical instability. Indeed, mutations of critical residues located on the Fc dimerization interface allowed the expression of fully stable EPO monomeric Fc-fusion proteins. We discuss the limitations of Fc-fusion technology in N. benthamiana transient expression systems and suggest strategies to optimize the Fc-based scaffolds on their folding and aggregation resistance in order to improve the stability.


1995 ◽  
Vol 29 (1) ◽  
pp. 3-4
Author(s):  
Tracey Langsdale ◽  
Carlene Todd
Keyword(s):  

1980 ◽  
Vol 24 (02) ◽  
pp. 101-113 ◽  
Author(s):  
Owen F. Hughes ◽  
Farrokh Mistree ◽  
Vedran Žanic

A practical, rationally based method is presented for the automated optimum design of ship structures. The method required the development of (a) a rapid, design-oriented finite-element program for the analysis of ship structures; (b) a comprehensive mathematical model for the evaluation of the capability of the structure; and (c) a cost-effective optimization algorithm for the solution of a large, highly constrained, nonlinear redesign problem. These developments have been incorporated into a program called SHIPOPT. The efficiency and robustness of the method is illustrated by using it to determine the optimum design of a complete cargo hold of a general-purpose cargo ship. The overall dimensions and the design loads are the same as those used in the design of the very successful SD14 series of ships. The redesign problem contains 94 variables, a nonlinear objective function, and over 500 constraints of which approximately half are non-linear. Program SHIPOPT required approximately eight minutes of central processing unit time on a CDC CYBER 171 to determine the optimum design.


2019 ◽  
Vol 4 (2) ◽  
pp. e001248
Author(s):  
Helen Saxenian ◽  
Nahad Sadr-Azodi ◽  
Miloud Kaddar ◽  
Kamel Senouci

Immunisation is a cornerstone to primary health care and is an exceptionally good value. The 14 low-income and middle-income countries in the Middle East and North Africa region make up 88% of the region’s population and 92% of its births. Many of these countries have maintained high immunisation coverage even during periods of low or negative economic growth. However, coverage has sharply deteriorated in countries directly impacted by conflict and political unrest. Approximately 1.3 million children were not completely vaccinated in 2017, as measured by third dose of diphtheria–pertussis–tetanus vaccine. Most of the countries have been slow to adopt the newer, more expensive life-saving vaccines mainly because of financial constraints and the socioeconomic context. Apart from the three countries that have had long-standing assistance from Gavi, the Vaccine Alliance, most countries have not benefited appreciably from donor and partner activities in supporting their health sector and in achieving their national and subnational immunisation targets. Looking forward, development partners will have an important role in helping reconstruct health systems in conflict-affected countries. They can also help with generating evidence and strategic advocacy for high-priority and cost-effective services, including immunisation. Governments and ministries of health would ensure important benefits to their populations by investing further in their immunisation programmes. Where possible, the health system can create and expand fiscal space from efficiency gains in harmonising vaccine procurement mechanisms and service integration; broader revenue generation from economic growth; and reallocation of government budgets to health, and from within health, to immunization.


Sign in / Sign up

Export Citation Format

Share Document