Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Ghosh, Subrata; Duigou, Gregory J.

doi:10.1158/0008-5472.can-05-0581

Cited by 44 publications

(9 citation statements)

References 51 publications

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“…Although these AdVs use cancer-specific promoters, the adenoviruses replicate in the target cells and produce damaging effects through adenovirus gene expression in the target and surrounding cells. Although it has been reported that replication of E1-dereted AdV can be detected by Southern hybridization technique in HeLa cells at a higher MOI (42) and in other certain cells two weeks after infection (43), the replication level seemed too low to influence on the results described here.…”

Section: Discussioncontrasting

confidence: 58%

High-level expression by tissue/cancer-specific promoter with strict specificity using a single-adenoviral vector

Kanegae

Terashima

Kondo

et al. 2010

Nucleic Acids Research

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Tissue-/cancer-specific promoters for use in adenovirus vectors (AdVs) are valuable for elucidating specific gene functions and for use in gene therapy. However, low activity, non-specific expression and size limitations in the vector are always problems. Here, we developed a ‘double-unit’ AdV containing the Cre gene under the control of an α-fetoprotein promoter near the right end of its genome and bearing a compact ‘excisional-expression’ unit consisting of a target cDNA ‘upstream’ of a potent promoter between two loxPs near the left end of its genome. When Cre was expressed, the expression unit was excised as a circular molecule and strongly expressed. Undesired leak expression of Cre during virus preparation was completely suppressed by a dominant-negative Cre and a short-hairpin RNA against Cre. Using this novel construct, a very strict specificity was maintained while achieving a 40- to 90-fold higher expression level, compared with that attainable using a direct specific promoter. Therefore, the ‘double-unit’ AdV enabled us to produce a tissue-/cancer-specific promoter in an AdV with a high expression level and strict specificity.

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Section: Discussioncontrasting

confidence: 58%

High-level expression by tissue/cancer-specific promoter with strict specificity using a single-adenoviral vector

Kanegae

Terashima

Kondo

et al. 2010

Nucleic Acids Research

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“…Second, the PSMA aptamer—that is selected to bind to a particular transmembrane protein overexpressed in prostate cancer cells [ 26 ] —enables cell targeting and efficient internalization of the cargos through an endocytic pathway. [ 27,28 ] Finally, there is a growing number of studies showing that cholesterol‐anchored nanostructures can reversibly associate with and laterally diffuse on lipid bilayers of the plasma membrane. [ 29 ] Given this, we speculated that the decoration of DNF with hydrophobic cholesterol [ 30 ] would mimic the amphiphilic nature of the cell membrane, [ 29,31 ] leading to a synergistic effect in cellular uptake together with the receptor‐binding aptamers.…”

Section: Figurementioning

confidence: 99%

Tumor‐Targeting Cholesterol‐Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing

Kim

et al. 2021

Advanced Materials

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Probing endogenous molecular profiles is of fundamental importance to understand cellular function and processes. Despite the promise of programmable nucleic‐acid‐based aptasensors across the breadth of biomolecular detection, target‐responsive aptasensors enabling intracellular detection are as of yet infrequently realized. Several challenges remain, including the difficulties in quantification/normalization of quencher‐based intensiometric signals, stability issues of the probe architecture, and complex sensor operations often necessitating extensive structural modeling. Here, the biomimetic crystallization‐empowered self‐assembly of a tumor‐targetable DNA–inorganic hybrid nanocomposite aptasensor is presented, which enables Förster resonance energy transfer (FRET)‐based quantitative interpretation of changes in the cellular target abundance. Leveraging the design programmability and high‐throughput fabrication of rolling circle amplification‐driven DNA nanoarchitecture, this designer platform offers a method to self‐assemble a robust nanosensor from a multifunctionality‐encoded template that includes a cell‐targeting aptamer, a ratiometric aptasensor, and a cholesterol‐decorating element. Taking prostate cancer cells and intracellular adenosine triphosphate molecules as a model system, a synergistic effect in the targeted delivery by cholesterol and aptamers, and the feasibility of quantitative intracellular aptasensing are demonstrated. It is envisioned that this approach provides a highly generalizable strategy across wide‐ranging target systems toward a biologically deliverable nanosensor that enables quantitative monitoring of the abundance of endogenous biomolecules.

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“…Thus, the development of novel and improved therapeutic approaches is necessary. Adenoviruses-mediated gene therapy strategies have been proposed and studied in clinical trials; however, results with traditional adenovirus serotype 5 (Ad5)-based vectors have been disappointing (13)(14)(15)(16). A significant reason for the disappointing outcome with Ad5-based vectors is likely the low expression of the coxsackievirus and adenovirus receptor (CAR) on GBM cells.…”

Section: Introductionmentioning

confidence: 99%

A Capsid-Modified, Conditionally Replicating Oncolytic Adenovirus Vector Expressing TRAIL Leads to Enhanced Cancer Cell Killing in Human Glioblastoma Models

et al. 2007

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Glioblastoma multiforme (GBM) is the most aggressive brain tumor, and patients rarely survive for more than 2 years. Gene therapy may offer new treatment options and improve the prognosis for patients with GBM. Adenovirus-mediated gene therapy strategies for brain tumors have been limited by inefficient gene transfer due to low expression of the adenovirus serotype 5 (Ad5) receptor. We have used an adenovirus vector that specifically replicates in tumor cells and uses an Ad5 capsid and the adenovirus serotype (Ad35) fiber for efficient infection of malignant tumor cells. This vector also expresses adenovirus E1A and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a tumor-specific manner. Here, we show that this oncolytic vector (Ad5/Ad35.IR-E1A/TRAIL) efficiently infects the GBM tumor cell lines SF767, T98G, and U-87 MG. Tumor cell killing was markedly enhanced with Ad5/Ad35.IR-E1A/TRAIL compared with wildtype Ad5 and Ad35 virus or Ad5/Ad35.IR-E1A-vectors without TRAIL expression in vitro. In vivo experiments using s.c. xenografted U-87 MG cells in NOD/SCID mice showed a significant growth delay of tumors after i.t. injection of Ad5/Ad35.IR-E1A/TRAIL, whereas adenovirus wild-type injections showed only marginal or no effect. Our findings indicate that the use of a capsid-modified adenoviral vector, in combination with TRAIL expression, is a promising novel approach for gene therapy of glioblastoma. [Cancer Res 2007;67(18):8783-90]

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Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Cited by 44 publications

References 51 publications

High-level expression by tissue/cancer-specific promoter with strict specificity using a single-adenoviral vector

High-level expression by tissue/cancer-specific promoter with strict specificity using a single-adenoviral vector

Tumor‐Targeting Cholesterol‐Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing

A Capsid-Modified, Conditionally Replicating Oncolytic Adenovirus Vector Expressing TRAIL Leads to Enhanced Cancer Cell Killing in Human Glioblastoma Models

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