Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts

Quan, Wei; Liu, Zhaoyu; Fei, Yujie; Peng, Dan; Zuo, Houjuan; Huang, Xiaolin; Liu, Zhengxiang; Zhang, Xin

doi:10.1007/s11596-011-0148-2

Cited by 4 publications

(1 citation statement)

References 26 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytomegalovirus (CMV) promoter is commonly used to drive gene expression as it is constitutively active and results in high levels of expression in a wide range of tissues 25 . The use of tissue specific promoters in gene therapy has been explored to treat liver carcinomas 10, 34 , cardiac ischemia 29 , and neurological disorders 4 . However, using tissue and injury specific targeting of transgenes to distinct afferent populations for the treatment of pain has not been explored.…”

Section: Introductionmentioning

confidence: 99%

Injury-Specific Promoters Enhance Herpes Simplex Virus–Mediated Gene Therapy for Treating Neuropathic Pain in Rodents

Smith

Paige

Velázquez

et al. 2015

The Journal of Pain

View full text Add to dashboard Cite

Chronic neuropathic pain is often difficult to treat with current pain medications. Gene therapy is currently being explored as a therapeutic approach for the treatment of neuropathic and cancer pain. In this study we sought to use an injury-specific promoter to deliver the mu opioid receptor (MOR) transgene such that expression would only occur during the injured state in response to release of injury-specific galanin. To determine whether an injury specific promoter can produce neuron-specific MOR expression and enhanced antinociception we compared animals infected with a galanin promoter virus (galMOR) or a human cytomegalovirus (CMV) promoter virus. (cmvMOR). In behavioral assays, we found an earlier onset and a larger magnitude of antinociception in animals infected with galMOR compared to cmvMOR. Immunohistochemistry of dorsal root ganglion (DRG) neurons revealed a significant increase in MOR positive staining in cmvMOR and galMOR treated mice. Spinal cord sections from galMOR treated mice showed a greater increase in density but not area of MOR positive staining. These results suggest that using injury-specific promoters to drive gene expression in primary afferent neurons can influence the onset and magnitude of antinociception in a rodent model of neuropathic pain and can be used to upregulate MOR expression in populations of neurons that are potentially injury specific. Perspective An injury specific promoter (galMOR) was used to drive MOR expression in a population- and injury- specific manner. GalMOR increased antinociception and density of MOR staining in spinal cord. This article presents evidence that promoter selection is an important component in successful gene expression in an injury- and population-specific manner.

show abstract

Section: Introductionmentioning

confidence: 99%

Injury-Specific Promoters Enhance Herpes Simplex Virus–Mediated Gene Therapy for Treating Neuropathic Pain in Rodents

Smith

Paige

Velázquez

et al. 2015

The Journal of Pain

View full text Add to dashboard Cite

show abstract

CD151 promotes proliferation and migration of PC3 cells via the formation of CD151-integrin α3/α6 complex

Yang

Lin

et al. 2012

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

Over-expression of CD151 was found to be associated with metastasis and poor prognosis of prostatic carcinoma. This study was designed to examine the mechanism by which CD151 promotes the proliferation and migration of prostatic cancer cells. The pAAV-CD151, pAAV-GFP and pAAV-CD151-AAA mutant plasmids were constructed and used to transiently transfect PC3 cells (a prostatic carcinoma 3 cell line) by the mediation of Fugene HD. Then, the cells were assigned to control group, pAAV-GFP group, pAAV-CD151 group, and pAAV-CD151-AAA group respectively. Cell proliferation was evaluated by using the 3-[4,5-dimet-hylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method. Cell migration assay was performed by using Boyden chambers. The formation of CD151-integrin α3/α6 complex was determined by the method of co-immunoprecipitation. The protein expression levels of CD151 and extracellular signal-regulated kinase (ERK) were measured by Western blotting. The results showed that transfection of pAAV-CD151 or pAAV-CD151-AAA mutant increased the expression of CD151 protein in PC3 cells. Co-immunoprecipitation showed that more CD151-integrin α3/α6 complex was formed in the pAAV-CD151 group than in the control group, the pAAV-GFP group and the pAAV-CD151-AAA mutant group. Furthermore, the proliferative and migrating capacity of PC3 cells was substantially increased in the pAAV-CD151 group but inhibited in the pAAV-CD151-AAA mutant group. CD151 transfection increased the expression of phospho-ERK. Taken together, it was concluded that CD151 promotes the proliferation and migration of PC3 cells through the formation of CD151-integrin complex and the activation of phosphorylated ERK.

show abstract

Immune safety of a novel oncolytic mutant M1 after administration In Vivo

Jiang

Zhou

et al. 2012

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.

show abstract

Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts

Cited by 4 publications

References 26 publications

Injury-Specific Promoters Enhance Herpes Simplex Virus–Mediated Gene Therapy for Treating Neuropathic Pain in Rodents

Injury-Specific Promoters Enhance Herpes Simplex Virus–Mediated Gene Therapy for Treating Neuropathic Pain in Rodents

CD151 promotes proliferation and migration of PC3 cells via the formation of CD151-integrin α3/α6 complex

Immune safety of a novel oncolytic mutant M1 after administration In Vivo

Contact Info

Product

Resources

About