Large-Scale Production of Recombinant Adeno-Associated Viral Vectors

Author(s):  
Alejandro Negrete ◽  
Robert M. Kotin
Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1051
Author(s):  
Eduardo Martínez-Molina ◽  
Carlos Chocarro-Wrona ◽  
Daniel Martínez-Moreno ◽  
Juan A. Marchal ◽  
Houria Boulaiz

Lentiviral vectors (LVs) have gained value over recent years as gene carriers in gene therapy. These viral vectors are safer than what was previously being used for gene transfer and are capable of infecting both dividing and nondividing cells with a long-term expression. This characteristic makes LVs ideal for clinical research, as has been demonstrated with the approval of lentivirus-based gene therapies from the Food and Drug Administration and the European Agency for Medicine. A large number of functional lentiviral particles are required for clinical trials, and large-scale production has been challenging. Therefore, efforts are focused on solving the drawbacks associated with the production and purification of LVsunder current good manufacturing practice. In recent years, we have witnessed the development and optimization of new protocols, packaging cell lines, and culture devices that are very close to reaching the target production level. Here, we review the most recent, efficient, and promising methods for the clinical-scale production ofLVs.


2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Katharina B. Lauer ◽  
Ray Borrow ◽  
Thomas J. Blanchard

ABSTRACT The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors—proven safe and successful in veterinary vaccine applications—are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).


1993 ◽  
Vol 32 (1) ◽  
pp. 129-131
Author(s):  
Naureen Talha

The literature on female labour in Third World countries has become quite extensive. India, being comparatively more advanced industrially, and in view of its size and population, presents a pictures of multiplicity of problems which face the female labour market. However, the author has also included Mexico in this analytical study. It is interesting to see the characteristics of developing industrialisation in two different societies: the Indian society, which is conservative, and the Mexican society, which is progressive. In the first chapter of the book, the author explains that he is not concerned with the process of industrialisation and female labour employed at different levels of work, but that he is interested in forms of production and women's employment in large-scale production, petty commodity production, marginal small production, and self-employment in the informal sector. It is only by analysis of these forms that the picture of females having a lower status is understood in its social and political setting.


2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.


2018 ◽  
Vol 15 (4) ◽  
pp. 572-575 ◽  
Author(s):  
Ponnusamy Kannan ◽  
Samuel I.D. Presley ◽  
Pallikondaperumal Shanmugasundaram ◽  
Nagapillai Prakash ◽  
Deivanayagam Easwaramoorthy

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.


Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 241
Author(s):  
Shaden A. M. Khalifa ◽  
Eslam S. Shedid ◽  
Essa M. Saied ◽  
Amir Reza Jassbi ◽  
Fatemeh H. Jamebozorgi ◽  
...  

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.


Energies ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1940
Author(s):  
Muhammad Usman Naseer ◽  
Ants Kallaste ◽  
Bilal Asad ◽  
Toomas Vaimann ◽  
Anton Rassõlkin

This paper presents current research trends and prospects of utilizing additive manufacturing (AM) techniques to manufacture electrical machines. Modern-day machine applications require extraordinary performance parameters such as high power-density, integrated functionalities, improved thermal, mechanical & electromagnetic properties. AM offers a higher degree of design flexibility to achieve these performance parameters, which is impossible to realize through conventional manufacturing techniques. AM has a lot to offer in every aspect of machine fabrication, such that from size/weight reduction to the realization of complex geometric designs. However, some practical limitations of existing AM techniques restrict their utilization in large scale production industry. The introduction of three-dimensional asymmetry in machine design is an aspect that can be exploited most with the prevalent level of research in AM. In order to take one step further towards the enablement of large-scale production of AM-built electrical machines, this paper also discusses some machine types which can best utilize existing developments in the field of AM.


Author(s):  
Yuting Luo ◽  
Zhiyuan Zhang ◽  
Fengning Yang ◽  
Jiong Li ◽  
Zhibo Liu ◽  
...  

Large-scale production of green hydrogen by electrochemical water splitting is considered as a promising technology to address critical energy challenges caused by the extensive use of fossil fuels. Although nonprecious...


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