scholarly journals CRISPR/Cas9 and cancer

2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Nora Mimoune ◽  
Mohamed Wail Bahouh ◽  
Said Boukhechem ◽  
Djamel Khelef ◽  
Rachid Kaidi
Keyword(s):  
Cancer Research ◽  
Clinical Trials ◽  
Immune System ◽  
Genome Engineering ◽  
Adaptive Immune System ◽  
Powerful Method ◽  
Efficient Technology ◽  
Adaptive Immune ◽  
Mouse Models Of Cancer ◽  
The Impact

CRISPR/Cas9 has become a powerful method for making changes to the genome of many organisms. First discovered in bacteria as part of an adaptive immune system, CRISPR/Cas9 and modified versions have found widespread use in genome engineering and in the activation or repression of gen expression. As such, CRISPR/Cas9 promises to accelerate cancer research by providing an efficient technology to dissect mechanisms of tumorigenesis, identify targets for drug development, and possibly arm cells for cell-based therapies. Here, we review the current applications of the CRISPR/Cas9 technology for cancer research and therapy. We highlight the impact of CRISPR/Cas9 in generating organoid and mouse models of cancer. Finally, we provide an overview of the first clinical trials applying CRISPR/Cas9 as a therapeutic approach against cancer.

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1314 ◽  
Author(s):  
Sen ◽  
Almuslehi ◽  
Gyengesi ◽  
Myers ◽  
Shortland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Immune System ◽  
Adaptive Immune System ◽  
Synaptic Function ◽  
Adaptive Immune ◽  
Splenic Atrophy ◽  
The Impact ◽  
The Brain ◽  
Inside Out

Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

scholarly journals T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

2020 ◽  
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

AbstractBackground: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective: To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals The Impact of Nanoparticles on the Immune System: A Gray Zone of Nanomedicine

2021 ◽  
Vol 5 (1) ◽  
pp. 19-33
Author(s):  
Priyanka Ray ◽  
Noor Haideri ◽  
Inamul Haque ◽  
Omar Mohammed ◽  
Saborni Chakraborty ◽  
...  
Keyword(s):  
Immune System ◽  
Genetic Disorders ◽  
Survival Rates ◽  
Adaptive Immune System ◽  
Gray Zone ◽  
Meaningful Change ◽  
Surface Receptors ◽  
Adaptive Immune ◽  
System A ◽  
The Impact

Since the early days marking the first use of nanomedicine in the early 80s, there has been a meaningful change in the scientific field involving the Fabrication, characterization, and application of nanomaterials to treat many diseases, including cancers and genetic disorders. As unique and attractive properties of this novel class of materials unraveled, significant advances and discoveries were made over time. Addressing several challenges posed by conventional therapy, which were the only available treatment option for ailing patients, nanomedicine provided enhanced benefits, including reduced dosing, improved pharmacokinetics, and superior targeting efficiency. Several such formulations have successfully made their way to clinics and have shown promise in prolonging terminally ill patient populations' survival rates. However, the complex immune system and its various components, including various proteins and surface receptors, have made nanomaterials' journey from benchtop to the bedside a treacherous one. The innate and adaptive immune system interactions with nanomaterials are still under investigation and full of mysteries. This review highlights the various aspects of therapeutic nanocarriers and their current understanding of their immune systems' interactions.

scholarly journals Prokaryotic genome expansion is facilitated by phages and plasmids but impaired by CRISPR

2018 ◽  
Author(s):  
Na L. Gao ◽  
Jingchao Chen ◽  
Martin J Lercher ◽  
Wei-Hua Chen
Keyword(s):  
Immune System ◽  
Genome Size ◽  
Negative Impact ◽  
Prokaryotic Genome ◽  
Adaptive Immune System ◽  
Bacterial Cells ◽  
Adaptive Immune ◽  
Genome Expansion ◽  
Prokaryotic Genomes ◽  
The Impact

AbstractBacteriophages and plasmids can introduce novel DNA into bacterial cells, thereby creating an opportunity for genome expansion; conversely, CRISPR, the prokaryotic adaptive immune system, which targets and eliminates foreign DNAs, may impair genome expansions. Recent studies presented conflicting results over the impact of CRISPR on genome expansion. In this study, we assembled a comprehensive dataset of prokaryotic genomes and identified their associations with phages and plasmids. We found that genomes associated with phages and/or plasmids were significantly larger than those without, indicating that both phages and plasmids contribute to genome expansion. Genomes were increasingly larger with increasing numbers of associated phages or plasmids. Conversely, genomes with CRISPR systems were significantly smaller than those without, indicating that CRISPR has a negative impact on genome size. These results confirmed that on evolutionary timescales, bacteriophages and plasmids facilitate genome expansion, while CRISPR impairs such a process in prokaryotes. Furthermore, our results also revealed that CRISPR systems show a strong preference for targeting phages over plasmids.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune
Sign in / Sign up

Export Citation Format

Share Document