Inhibition of Telomerase Activity Using an EGFP-Intron Splicing System Encoding Multiple RNAi Sequences

Sakiragaoglu, Onur; Munn, Alan Leslie

doi:10.1007/s12033-016-9982-6

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Silencing or inhibition of TERT or TERC activity are further applications within the realm of gene therapy that exploit constitutive activation of TERT in cancer [73][74][75].For example, siRNA or antisense RNA targeting TERT has been a popular gene therapy [76][77][78][79][80][81], with a small number of studies examining various strategies (such as expression of the c-terminal TERT polypeptide (hTERTC27) [61,82,83], CRISPR/Cas9 targeting an oncogenic TERT promoter mutant allele that allows constitutive activation in cancer [84], or microRNA-mediated downregulation of TERT by targeting the 30 -UTR. These methods, in general, promote cellular senescence, cause apoptotic tumor cell death, and slow tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Telomerase Gene Therapy: A Remission Towards Cancer

Quazi¹

2021

Preprint

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Telomerase is an enzyme which is culpable for the aliment and stability of telomeres. It also maintains the genomic integrity and chromosomal stability. The progressive shortening of telomeres may cause chromosomal instability and alternation in the telomerase. It may cause telomere attrition which can lead to oncogenic incidence in human. Cancer is a disease which is induced by genetic alternations in genes. The genetic mutation within the hTERT is a common type of scenario which is generally found above 90 percent of cancer. In cancer, the length of telomere and the activity of telomerase are very important for cancer cells to proliferate and also for the survival of tumors. Cancer cells regulate through several pathways to increase telomerase activity. There have been several advancements developed to inhibit the telomerase activity in cancer cell but the repercussion of those has demonstrated many adverse effects. Research on AAVs mediated telomerase gene therapy has demonstrated prominent outcomes in animal trials. Thus, it has the potential to bring significance shine in the telomerase cancer therapeutics. Here, in this review article we have analyzed studies related to telomerase gene therapeutics to cure cancer. We also have summarized the telomerase function and mechanism of action to cause cancer. Moreover, other current development in the clinical advances of telomerase inhibition in cancer is described.

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Section: Discussionmentioning

confidence: 99%

Telomerase Gene Therapy: A Remission Towards Cancer

Quazi¹

2021

Preprint

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“…The plasmid used for overexpressing RPMS1 long non-coding RNA was 17ADVGAP, the vector with the entire long non-coding RPMS1 cDNA, which was ordered from GeneArt. The sequence encoding miR-BARTs clusters was cloned from C666-1 and inserted into the blue fluorescent protein gene as an intron 43 .…”

Section: Cells Plasmids and Chemicalsmentioning

confidence: 99%

Landscape of Epstein-Barr virus gene expression and perturbations in cancer

Tang,

Tian,

Xie

et al. 2024

Preprint

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Epstein-Barr virus (EBV) is the causative agent for multiple neoplastic diseases of epithelial and lymphocytic origin1-3. The heterogeneity of the viral elements expressed and the mechanisms by which these coding and non-coding genes maintain cancer cell properties in vivo remain elusive4,5. Here we conducted a multi-modal transcriptomic analysis of EBV-associated neoplasms and identified that the ubiquitously expressed RPMS1 non-coding RNAs support cancer cell properties by disruption of the interferon response. Our map of EBV expression shows a variable, but pervasive expression of BNLF2 discerned from the overlapping LMP1 RNA in bulk sequencing data. Using long-read single-molecule sequencing, we identified three new viral elements within the RPMS1 gene. Furthermore, single-cell sequencing datasets allowed for the separation of cancer cells and healthy cells from the same tissue biopsy and the characterization of a microenvironment containing interferon gamma excreted by EBV-stimulated T-lymphocytes. In comparison with healthy epithelium, EBV-transformed cancer cells exhibited increased proliferation and inhibited immune response induced by the RPMS1-encoded microRNAs. Our atlas of EBV expression shows that the EBV-transformed cancer cells express high levels of non-coding RNAs originating from RPMS1 and that the oncogenic properties are maintained by RPMS1 microRNAs. Through bioinformatic disentanglement of single cells from cancer tissues we identified a positive feedback loop where EBV-activated immune cells stimulate cancer cells to proliferate, which in turn undergo viral reactivation and trigger an immune response.

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“…Alternative applications within the scope of gene therapy exploiting constitutive activation of TERT in cancer utilize silencing or inhibition of TERT or TERC activity [76,77,78]. For example, siRNA or antisense RNA targeting TERT has been an actively investigated gene therapeutic of choice [79,80,81,82,83,84], with a small number of reports exploring different strategies (such as expression of c-terminal TERT polypeptide (hTERTC27) [85,86,87], CRISPR/Cas9 targeting an oncogenic TERT promoter mutant allele that enables constitutive activation in cancer [88], or microRNA-mediated downregulation of TERT by targeting of the 3′-UTR region [89]). In general, these approaches promote cellular senescence, induce apoptotic tumor cell death, and attenuate the rate of proliferation.…”

Section: Anticancer Applicationmentioning

confidence: 99%

Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases

Hong

Yun²

2019

Cells

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Modulation of telomerase maintenance by gene therapy must meet two polarizing requirements to achieve different therapeutic outcomes: Anti-aging/regenerative applications require upregulation, while anticancer applications necessitate suppression of various genes integral to telomere maintenance (e.g., telomerase, telomerase RNA components, and shelterin complex). Patients suffering from aging-associated illnesses often exhibit telomere attrition, which promotes chromosomal instability and cellular senescence, thus requiring the transfer of telomere maintenance-related genes to improve patient outcomes. However, reactivation and overexpression of telomerase are observed in 85% of cancer patients; this process is integral to cancer immortality. Thus, telomere-associated genes in the scope of cancer gene therapy must be inactivated or inhibited to induce anticancer effects. These contradicting requirements for achieving different therapeutic outcomes mean that any vector-mediated upregulation of telomere-associated genes must be accompanied by rigorous evaluation of potential oncogenesis. Thus, this review aims to discuss how telomere-associated genes are being targeted or utilized in various gene therapy applications and provides some insight into currently available safety hazard assessments.

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Inhibition of Telomerase Activity Using an EGFP-Intron Splicing System Encoding Multiple RNAi Sequences

Cited by 4 publications

References 11 publications

Telomerase Gene Therapy: A Remission Towards Cancer

Telomerase Gene Therapy: A Remission Towards Cancer

Landscape of Epstein-Barr virus gene expression and perturbations in cancer

Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases

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