Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

Mao, Xiao‐Yuan; Dai, Jinxiang; Zhou, Hong‐Hao; Liu, Zhao‐Qian; Jin, Wei‐Lin

doi:10.18632/oncotarget.8075

Cited by 20 publications

(18 citation statements)

References 103 publications

(101 reference statements)

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“…Glioma GEMMs based on CRISPR-Cas9 have demonstrated the versatility and efficiency of this technology for in vivo tumour models [86]. For example, in utero electroporation of the developing prosencephalon of multiple plasmids encoding Cas9 together with sgRNAs targeting Nf1 , Pten , and Trp53 led to the confirmed loss of these genes, and subsequent development of tumours histologically resembling human GBMs [87].…”

Section: Crispr-cas9 Genetic Engineering and Screens In Micementioning

confidence: 99%

Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries

Noorani

2019

Cancers

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The most common brain tumours, gliomas, have significant morbidity. Detailed biological and genetic understanding of these tumours is needed in order to devise effective, rational therapies. In an era generating unprecedented quantities of genomic sequencing data from human cancers, complementary methods of deciphering the underlying functional cancer genes and mechanisms are becoming even more important. Genetically engineered mouse models of gliomas have provided a platform for investigating the molecular underpinning of this complex disease, and new tools for such models are emerging that are enabling us to answer the most important questions in the field. Here, I discuss improvements to genome engineering technologies that have led to more faithful mouse models resembling human gliomas, including new cre/LoxP transgenic lines that allow more accurate cell targeting of genetic recombination, Sleeping Beauty and piggyBac transposons for the integration of transgenes and genetic screens, and CRISPR-cas9 for generating genetic knockout and functional screens. Applications of these technologies are providing novel insights into the functional genetic drivers of gliomagenesis, how these genes cooperate with one another, and the potential cells-of-origin of gliomas, knowledge of which is critical to the development of targeted treatments for patients in the clinic.

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Section: Crispr-cas9 Genetic Engineering and Screens In Micementioning

confidence: 99%

Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries

Noorani

2019

Cancers

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“…Cas9 is guided by sgRNA which helps in recognition of complementary target sequence flanked by PAM sequence and thus, it guide Cas9 for cleavage. Out of different types of CRISPR/Cas9, type II system is widely used because of involvement of reduced number of Cas enzymes ( 137 ). Multiple repeated sequences (~21–28 bp) in CRISPR loci interspersed by variable spacer sequence holding correspondence to sequence within foreign genetic elements (protospacer) and Cas9 genes that are placed alongside these loci.…”

Section: Gene Editing Tools For Hiv Treatmentmentioning

confidence: 99%

“…Cas9 has two domains, i.e., HNH and RuvC, for cleavage of complementary (target) sequence and non-complementary (non-target) strand, respectively. These double stranded breaks are then repaired by cellular repair pathways: either non-homologous ends joining (NHEJ) or homologous directed repair ( 137 ).…”

Section: Gene Editing Tools For Hiv Treatmentmentioning

confidence: 99%

HIV Diagnosis and Treatment through Advanced Technologies

Zulfiqar

Javed

Sumbal

et al. 2017

Front. Public Health

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Human immunodeficiency virus (HIV) is the chief contributor to global burden of disease. In 2010, HIV was the fifth leading cause of disability-adjusted life years in people of all ages and leading cause for people aged 30–44 years. It is classified as a member of the family Retroviridae and genus Lentivirus based on the biological, morphological, and genetic properties. It infects different cells of the immune system, such as CD4+ T cells (T-helper cells), dendritic cells, and macrophages. HIV has two subtypes: HIV-1 and HIV-2. Among these strains, HIV-1 is the most virulent and pathogenic. Advanced diagnostic methods are exploring new ways of treatment and contributing in the reduction of HIV cases. The diagnostic techniques like PCR, rapid test, EIA, p24 antigen, and western blot have markedly upgraded the diagnosis of HIV. Antiretroviral therapy and vaccines are promising candidates in providing therapeutic and preventive regimes, respectively. Invention of CRISPR/Cas9 is a breakthrough in the field of HIV disease management.

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“…This eliminates the impact of the natural immune system in either the establishment of the tumor or the effect of the therapy. 12 Hence, research into immunotherapy in murine models can be quite a challenge, not to mention the difficulty inherent in the translation of information from an immunocompromised model into a relatively immunocompetent patient. However, there is a strategy for creation of immunocompetent tumor bearing murine models via lentiviral vectors that is occasionally used, though it uncommonly leads to cortical tumors (the expected location of most aggressive gliomas).…”

Section: Brain Tumor Surrogatesmentioning

confidence: 99%

Thermal Therapy Approaches for Treatment of Brain Tumors in Animals and Humans

Bredlau

McCrackin

Motamarry

et al. 2016

Crit Rev Biomed Eng

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Primary brain tumors are often aggressive, with short survival from time of diagnosis even with standard of care therapies such as surgery, chemotherapy, and radiation therapy. Thermal therapies have been extensively investigated as both primary and adjuvant therapy. Although thermal therapies are not yet widely used clinically, there have been several promising approaches demonstrated in both animals and humans. This review presents thermal therapy approaches in animal and human studies, including both hyperthermia (temperatures ~42°C–45°C) and thermal ablation (temperatures > 50°C). Hyperthermia is primarily used as adjuvant to chemotherapy and radiotherapy, and is the most widely studied radiation sensitizer where enhanced efficacy has been shown in human patients with brain cancer. Hyperthermia has additional beneficial effects such as immunogenic effects, and opening of the blood-brain barrier to potentially enhance drug delivery, for example in combination with nanoparticle drug delivery systems. Thermal ablation uses high temperatures for direct local tumor destruction, and it found its way into clinical use as laser interstitial thermal therapy (LITT). This review presents various hyperthermia and ablation approaches, including a review of different devices and methods that have been used for thermal therapies, such as radiofrequency/microwaves, laser, high-intensity focused ultrasound, and magnetic nanoparticles. Current research efforts include the combination of advanced thermal therapy devices, such as focused ultrasound with radiation, as well as the use of thermal therapies to enhance chemotherapy delivery across the blood-brain barrier.

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Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

Cited by 20 publications

References 103 publications

Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries

Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries

HIV Diagnosis and Treatment through Advanced Technologies

Thermal Therapy Approaches for Treatment of Brain Tumors in Animals and Humans

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