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

Oscillations and Long-Lasting Correlations in a Model of the Lateral Geniculate Nucleus and Visual Cortex

2000 ◽  
Vol 84 (4) ◽  
pp. 1863-1868 ◽  
Author(s):  
Kyle L. Kirkland ◽  
Adam M. Sillito ◽  
Helen E. Jones ◽  
David C. West ◽  
George L. Gerstein
Keyword(s):  
Experimental Data ◽  
Visual Cortex ◽  
Cell Membrane ◽  
Lateral Geniculate Nucleus ◽  
Feedback Inhibition ◽  
Frequency Range ◽  
Lateral Geniculate ◽  
Low Threshold ◽  
Thalamocortical System

We have previously developed a model of the corticogeniculate system to explore cortically induced synchronization of lateral geniculate nucleus (LGN) neurons. Our model was based on the experiments of Sillito et al. Recently Brody discovered that the LGN events found by Sillito et al. correlate over a much longer period of time than expected from the stimulus-driven responses and proposed a cortically induced slow covariation in LGN cell membrane potentials to account for this phenomenon. We have examined the data from our model, and we found, to our surprise, that the model shows the same long-term correlation. The model's behavior was the result of a previously unsuspected oscillatory effect, not a slow covariation. The oscillations were in the same frequency range as the well-known spindle oscillations of the thalamocortical system. In the model, the strength of feedback inhibition from the cortex and the presence of low-threshold calcium channels in LGN cells were important. We also found that by making the oscillations more pronounced, we could get a better fit to the experimental data.

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.

scholarly journals NMDAR-independent acetylcholine, serotonin, and norepinephrine mediated modulation of synaptic eligibility traces into LTD in mice visual cortex

2020 ◽  
Author(s):  
Shumsuzzaman Khan
Keyword(s):  
Visual Cortex ◽  
Ex Vivo ◽  
Brain Slices ◽  
Low Frequency ◽  
Decay Kinetics ◽  
Low Frequency Stimulation ◽  
Long Term Changes ◽  
Frequency Stimulation ◽  
Mouse Visual Cortex

AbstractIn reward-based learning, synaptic eligibility traces are a well-defined theoretical solution for the conversion of initial co-activation of pre and postsynaptic neurons into long-term changes in synaptic strength by reward-linked neuromodulators. However, the types of neuromodulators involved in such a phenomenon in mouse visual cortex remain unknown. To characterize the Ex vivo condition, we used optogenetic stimulation of channelrhodopsin-(ChR2) expressing Cre/Ai32(ChR2-eYFP); Tph2-Cre/Ai32(ChR2-eYFP); Thi-Cre/Ai32(ChR2-eYFP) homozygous mice, which release acetylcholine, serotonin, and norepinephrine, respectively. With these mice it is possible to measure the transformation of eligibility traces into long-term changes by endogenous neuromodulators. Here we delineated that layer 2/3 neurons in the visual cortex showed no LTD after conditioning with paired-pulse low-frequency stimulation (ppLFS; 2Hz, 15 min). However, if conditioning was paired with acetylcholine, serotonin, or norepinephrine release upon 473 nm optical stimulation in brain slices, LTD occurs in every case. Thus, our data suggests a new pathway to connect the gap between stimulus and reward. Moreover, we found that stimulation by theta-glass or metal stimulators evoked IPSC traces with the same amplitudes but differences in decay kinetics, further questioning the appropriate use of stimulators in brain slices for evoking an event.

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.

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