Squalene/polyethylenimine based non-viral vectors: synthesis and use in systems for sustained gene release

2018 ◽  
Vol 9 (9) ◽  
pp. 1072-1081 ◽  
Author(s):  
Geta David ◽  
Lilia Clima ◽  
Manuela Calin ◽  
Cristina Ana Constantinescu ◽  
Mihaela Balan-Porcarasu ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Gene Carriers ◽  
Efficient Gene ◽  
3D Matrix ◽  
Matrix Yielding ◽  
Dna Release

New squalene/BPEI conjugates, acting as efficient gene carriers, were included in the 3D matrix, yielding tunable DNA release and long-term bioavailability.

pH-Sensitive Pentablock Copolymer Nanocapsules as Nontoxic and Efficient Gene Carriers

2011 ◽  
Vol 11 (6) ◽  
pp. 789-796 ◽  
Author(s):  
Min Sang Lee ◽  
Yeon Lim Jang ◽  
Dai Phu Huynh ◽  
Cong Truc Huynh ◽  
Yuhan Lee ◽  
...  
Keyword(s):  
Ph Sensitive ◽  
Gene Carriers ◽  
Efficient Gene ◽  
Pentablock Copolymer

scholarly journals Rapid, long-term labeling of cells in the developing and adult rodent visual cortex using double-stranded adeno-associated viral vectors

2009 ◽  
Vol 69 (10) ◽  
pp. 674-688 ◽  
Author(s):  
Rebecca L. Lowery ◽  
Yu Zhang ◽  
Emily A. Kelly ◽  
Cassandra E. Lamantia ◽  
Brandon K. Harvey ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Viral Vectors

scholarly journals Sterile Abscess in the Myocardium after Direct Intramyocardial Injection Related to Gene Therapy in a Swine Model

2011 ◽  
Vol 2011 ◽  
pp. 1-2 ◽  
Author(s):  
Kiyotake Ishikawa ◽  
Dennis Ladage ◽  
Lisa Tilemann ◽  
Yoshiaki Kawase ◽  
Roger J. Hajjar
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Viral Vectors ◽  
Swine Model ◽  
Clinical Settings ◽  
Intramyocardial Injection ◽  
New Therapy ◽  
Sterile Abscess ◽  
Efficient Gene ◽  
Cardiac Gene

Cardiac gene therapy is one of the most promising approaches to cure patients with cardiac dysfunctions. Many ways of efficient gene transfer using viral vectors are tested, and some of them are already used in clinical settings. However, it is always important to be keenly alert to the possible complications when a new therapy is introduced. We present a case of myocardial sterile abscess in a swine model associated with a direct myocardial injection.

scholarly journals Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhan ◽  
Manish Muhuri ◽  
Phillip W. L. Tai ◽  
Guangping Gao
Keyword(s):  
Infectious Diseases ◽  
Neutralizing Antibodies ◽  
Viral Vectors ◽  
De Novo ◽  
Genomic Variation ◽  
Transduction Efficiency ◽  
Foreign Proteins ◽  
Repeated Dosing

Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.

scholarly journals Virus-Vectored Ebola Vaccines

Acta Naturae ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 4-11 ◽  
Author(s):  
I. V. Dolzhikova ◽  
E. A. Tokarskaya ◽  
A. S. Dzharullaeva ◽  
A. I. Tukhvatulin ◽  
D. V. Shcheblyakov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
West Africa ◽  
Protective Immunity ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Virus Disease ◽  
Genetically Engineered ◽  
Preclinical Trials

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

Abstract 603: Effective And Sustained ACE2 Delivery Using Minicircles Technology

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jan Wysocki ◽  
Philipp K Haber ◽  
Minghao Ye ◽  
Christoph Maier ◽  
Mark J Osborn ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Gene Replacement ◽  
Ang Ii ◽  
Hydrodynamic Approach ◽  
New Gene ◽  
Cloned Cdna ◽  
Dose Dependent ◽  
Delivery Technology

Chronic and sustained amplification of ACE2 activity in vivo has required the development of transgenic mice or the use of viral vectors. Minicircle is a new gene delivery technology which is resistant to gene silencing, and therefore represents an attractive platform for gene replacement strategies in vivo . Here we cloned cDNA of soluble mouse ACE2 into a circular expression cassette and the resulting ACE2 minicircle (MC) was injected to female FVB mice using iv. hydrodynamic approach (10ug or 30ug/mouse). At 3-7d after MC administration, serum ACE2 activity in mice that received 10ug ACE2MC (n=9) was over 100-fold higher than in controls (n=9) (138±48 vs 0.7±0.2 RFU/uL/hr) and in ACE2MC mice (30ug) (n=8) was almost 1000-fold higher than in controls (n=14) (480 ±153 vs 0.5±0.1 RFU/uL/hr, respectively). Mice that received 10 ug ACE2MC were followed for consecutive serum ACE2 activity monitoring, BP measurements and plasma Ang levels. The increase in serum ACE2 activity was sustained until the end of the study (up to 82 days) (Figure). Despite such a marked increase in serum ACE2 activity in ACE2MC mice, conscious SBP was not different from controls (137±8 vs 138±7 mmHg, respectively). At the end of the study, when Ang II was infused acutely (0.2 ug/kg BW i.p.), the increase in plasma Ang II in ACE2MC mice was significantly reduced compared to control mice (915±154 vs 1420±131 fmoL/mL, p<0.05). Mini-circle delivery of ACE2 results in a dose-dependent and sustained long-term increase in serum ACE2 that efficiently degrades plasma Ang II. Extremely high increases in serum ACE2 activity do not reduce BP probably due to activation of non-ACE2 dependent compensatory Ang-hydrolyzing pathways.

scholarly journals Large-Scale Production of Lentiviral Vectors: Current Perspectives and Challenges

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1051
Author(s):  
Eduardo Martínez-Molina ◽  
Carlos Chocarro-Wrona ◽  
Daniel Martínez-Moreno ◽  
Juan A. Marchal ◽  
Houria Boulaiz
Keyword(s):  
Viral Vectors ◽  
Large Scale ◽  
Lentiviral Vectors ◽  
Good Manufacturing Practice ◽  
Scale Production ◽  
Gene Therapies ◽  
Packaging Cell ◽  
Large Scale Production ◽  
Target Production

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.

scholarly journals Gene Therapy: The Molecular Bandage for Treating Genetic Disorders

1970 ◽  
Vol 3 (1) ◽  
pp. 24-27
Author(s):  
Md Manjurul Karim
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Genetic Disorders ◽  
Clinical Status ◽  
Genetic Material ◽  
Review Article ◽  
Cell Tissue ◽  
Efficient Gene ◽  
Effective Delivery ◽  
A Cell

The concept of gene therapy involves the transfer of genetic material into a cell, tissue, or whole organ, with a view to curing a disease or at least improving the clinical status of a patient. Much of its success relies heavily on the development of an effective delivery system that is capable of efficient gene transfer in a variety of tissues, without causing any associated pathogenic effects. Viral vectors currently offer the best choice for efficient gene delivery, what has been discussed in this review article. Their performance and pathogenecity has been evaluated in animal models, and encouraging results form the basis for clinical trials to treat genetic disorders and acquired diseases. Despite some initial success in these trials, vector development remains a seminal concern for improved gene therapy technologies. DOI: http://dx.doi.org/10.3329/akmmcj.v3i1.10110 AKMMCJ 2012; 3(1): 24-27

scholarly journals Cyclopropenium Nanoparticles and Gene Transfection in Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 768
Author(s):  
Noam Y. Steinman ◽  
Luis M. Campos ◽  
Yakai Feng ◽  
Abraham J. Domb ◽  
Hossein Hosseinkhani
Keyword(s):  
Viral Vectors ◽  
Gene Transfection ◽  
Medical Science ◽  
Genetic Material ◽  
Mouse Fibroblast ◽  
Ethylene Imine ◽  
Efficient Gene ◽  
Poly Ethylene ◽  
First Time

Non-viral vectors for the transfection of genetic material are at the frontier of medical science. In this article, we introduce for the first time, cyclopropenium-containing nanoparticles as a cationic carrier for gene transfection, as an alternative to the common quaternary ammonium transfection agents. Cyclopropenium-based cationic nanoparticles were prepared by crosslinking poly(ethylene imine) (PEI) with tetrachlorocyclopropene. These nanoparticles were electrostatically complexed with plasmid DNA into nanoparticles (~50 nm). Their cellular uptake into F929 mouse fibroblast cells, and their eventual expression in vitro have been described. Transfection is enhanced relative to PEI with minimal toxicity. These cyclopropenium nanoparticles possess efficient gene transfection capabilities with minimal cytotoxicity, which makes them novel and promising candidates for gene therapy.

Bioreducible, hydrolytically degradable and targeting polymers for gene delivery

2017 ◽  
Vol 5 (18) ◽  
pp. 3253-3276 ◽  
Author(s):  
Ihsan Ullah ◽  
Khan Muhammad ◽  
Mary Akpanyung ◽  
Abdelilah Nejjari ◽  
Agnaldo Luis Neve ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Synthetic Gene ◽  
Suitable Alternative ◽  
Gene Carriers ◽  
Promising Application

Recently, synthetic gene carriers have been intensively developed owing to their promising application in gene therapy and considered as a suitable alternative to viral vectors because of several benefits.

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