Periocular Triamcinolone Enhances Intraocular Gene Expression after Delivery by Adenovirus

Park, Keun; Chuck, Roy S.; Cano, Marisol; Yew, Margaret; Nguyen, Viet Quoc; Parker, Jack; Mori, Keisuke; Gehlbach, Peter

doi:10.1167/iovs.07-0619

Cited by 4 publications

(5 citation statements)

References 49 publications

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“…This onset of gene expression is slower compared to adenovirus which peaks several days after the inoculation, both in the ear4 and in other tissues27. The delay in gene expression of BAAV is related to its molecular structure.…”

Section: Discussionmentioning

confidence: 89%

Gene transfer using bovine adeno-associated virus in the guinea pig cochlea

et al. 2009

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Gene transfer into cells of the cochlea is useful for both research and therapy. Bovine adeno-associated virus (BAAV) is a novel viral vector with potential for long term gene expression with little or no side effects. In this study we assessed transgene expression using BAAV with ß-actin-GFP as a reporter gene, in cochleae of normal and deafened guinea pigs. We used two different routes to inoculate the cochlea: scala media (SM) or scala tympani (ST). Auditory brainstem response assessments were done prior to inoculation, 7 days after inoculation and immediately prior to sacrifice, to assess the functional consequences of the treatment. We observed threshold shifts due to the surgical invasion, but no apparent pathology associated with the virus. Fourteen days after the injection, animals were sacrificed and cochleae assessed histologically. Epi-fluorescence showed that BAAV transduced the supporting cells of both normal and deafened animals through SM and ST inoculations. Transgene expression in cells of the membranous labyrinth following ST inoculation is an important outcome because of the greater feasibility of this route for future clinical application. BAAV facilitates efficient transduction of the membranous labyrinth epithelium with minimum pathogenicity and may become clinically applicable for inner ear gene therapy.

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Section: Discussionmentioning

confidence: 89%

Gene transfer using bovine adeno-associated virus in the guinea pig cochlea

et al. 2009

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“…Compared with adeno-associated viral (AAV) and retroviral delivery systems, adenoviral vectors, such as Ad5, clearly have many advantages. For example, adenoviral vectors have broad tropism allowing efficient targeting on many tissues of interest, a large payload capacity and high transduction efficiency relative to AAV system [10] and also a non-integrating characteristics which otherwise induce the risk of random mutagenesis of genome [10], [36] [36], [37], [38]. Moreover, adenoviral vectors can be engineered to cancer-selective oncolytic viruses [39], [40], [41], which are critical for clinical application of cancer gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

Zhao

et al. 2012

PLoS ONE

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BackgroundEMX2 is a human orthologue of the Drosophila empty spiracles homeobox gene that has been implicated in embryogenesis. Recent studies suggest possible involvement of EMX2 in human cancers; however, the role of EMX2 in carcinogenesis needs further exploration.ResultsIn this study, we reported that down-regulation of EMX2 expression was significantly correlated with EMX2 promoter hypermethylation in gastric cancer. Restoring EMX2 expression using an adenovirus delivery system in gastric cancer cell lines lacking endogenous EMX2 expression led to inhibition of cell proliferation and Wnt signaling pathway both in vitro and in a gastric cancer xenograft model in vivo. In addition, we observed that animals treated with the adenoviral EMX2 expression vector had significantly better survival than those treated with empty adenoviral vector.ConclusionOur study suggests that EMX2 is a putative tumor suppressor in human gastric cancer. The adenoviral-EMX2 may have potential as a novel gene therapy for the treatment of patients with gastric cancer.

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“…We found that subcutaneous Nutlin-3 injection in the nape revealed a modest (27.4%), but statistically significant, reduction (P < 0.05) in the amount of retinal vessels compared with those in sham-injected mice ( Figure 7, B and C). In an attempt to reduce systemic toxicity and improve delivery to the eye, we performed similar experiments and injected Nutlin-3 in the periorbital area under the fused eyelid (15). In these experiments, we found 43.8% fewer blood vessels compared with those in the sham-injected mice (P < 0.01) (Figure 7, D and E).…”

Section: Resultsmentioning

confidence: 90%

Retinal angiogenesis suppression through small molecule activation of p53

Chavala¹,

Kim²,

Tudisco³

et al. 2013

J. Clin. Invest.

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Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokinetargeted antiangiogenesis therapies.

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Periocular Triamcinolone Enhances Intraocular Gene Expression after Delivery by Adenovirus

Cited by 4 publications

References 49 publications

Gene transfer using bovine adeno-associated virus in the guinea pig cochlea

Gene transfer using bovine adeno-associated virus in the guinea pig cochlea

Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

Retinal angiogenesis suppression through small molecule activation of p53

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