Vascular Gene Therapy

Zuckerbraun, Brian S.; Tzeng, Edith

doi:10.1001/archsurg.137.7.854

Cited by 12 publications

(3 citation statements)

References 65 publications

(66 reference statements)

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“…It has the potential to overcome the side effects of immunosuppressive drugs by offering the possibility of ex vivo transduction of the transplant prior to implantation. AAV vectors are powerful tools for gene transfer directed into the vasculature, not only due to their low immunogenicity compared adenovirus and sustained expression of the delivered gene, 29 but also for their capacity to transduce both proliferating and non-proliferating cells 30 . To the best of our knowledge, this is the first report describing an AAV9-based therapy approach with the targeting peptide SLRSPP in a mouse model for TV.…”

Section: Discussionmentioning

confidence: 98%

AAV-Mediated Expression of AP-1-Neutralizing RNA Decoy Oligonucleotides Attenuates Transplant Vasculopathy in Mouse Aortic Allografts

Remes

Franz

Mohr

et al. 2019

Molecular Therapy - Methods & Clinical Development

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Transplant vasculopathy (TV), characterized by obstructive lesions in affected vessels, represents one of the long-term complications of cardiac transplantation. Activation of the transcription factor activator protein-1 (AP-1) is implicated in smooth muscle cell (SMC) phenotypic switch from contractile to synthetic function, increasing the migration and proliferation rate of these cells. We hypothesize that adeno-associated virus (AAV)-mediated delivery of an RNA hairpin AP-1 decoy oligonucleotide (dON) might effectively ameliorate TV severity in a mouse aortic allograft model. Aortic allografts from DBA/2 mice ex vivo transduced with modified AAV9-SLR carrying a targeting peptide within the capsid surface were transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A (10 mg/kg BW) was administered daily. AP-1 dONs were intracellularly expressed in the graft tissue as small hairpin RNA proved by fluorescent in situ hybridization. Explantation after 30 days and histomorphometric evaluation revealed that AP-1 dON treatment significantly reduced intima-to-media ratio by 41.5% (p < 0.05) in the grafts. In addition, expression of adhesion molecules, cytokines, as well as numbers of proliferative SMCs, matrix metalloproteinase-9-positive cells, and inflammatory cell infiltration were significantly decreased in treated aortic grafts. Our findings demonstrate the feasibility, efficacy, and specificity of the anti-AP-1 RNA dON approach for the treatment of allograft vasculopathy in an animal model. Moreover, the AAV-based approach in general provides the possibility to achieve a prolonged delivery of nucleic-acids-based therapeutics in to the blood vessel wall.

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Section: Discussionmentioning

confidence: 98%

AAV-Mediated Expression of AP-1-Neutralizing RNA Decoy Oligonucleotides Attenuates Transplant Vasculopathy in Mouse Aortic Allografts

Remes

Franz

Mohr

et al. 2019

Molecular Therapy - Methods & Clinical Development

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“…Local gene delivery to the peripheral circulation could be performed at the time of surgical exposure for intervention. Similarly, saphenous vein bypass grafts could be easily transduced ex vivo prior to implantation in the arterial circulation [63]. Intraoperative transfection of the vein graft combines intact tissue DNA transfer with the safety of ex vivo transfection.…”

Section: Specific Clinical Applications (Table 2)mentioning

confidence: 99%

Genetics and Gene Manipulation Therapy of Premature Coronary Artery Disease

2004

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Despite the notable recent scientific advances, our ability to detect and prevent premature coronary artery disease (CAD) remains limited, and the identification of patients at risk is yet to be based on objective scientific testing. Eliciting a family history of CAD currently remains the only available screening tool to identify patients with a genetic predisposition. The risk of CAD attributable to genes appears to be most significant at younger ages, and this may explain the lack of definite markers for the disease. Candidate gene association studies focusing on young patients with CAD will, therefore, be more likely to identify a true genetic risk. In this report, we review the known genetic risk factors for premature CAD. We also discuss the potential gene manipulation therapy of CAD as well as of vein graft atherosclerosis following coronary artery bypass surgery.

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“…Clinical research in therapeutic angiogenesis is ongoing for a variety of diseases like coronary artery diseases, peripheral arterial diseases and wound healing disorders. [6] The pro-angiogenesis therapies can be differentiated into three categories, namely, i) protein therapy,[7] ii) gene therapy[8] and, iii) cell based therapy which involved the implantation of specific cell types. Other than the above three therapies there are few therapies that have been used to induce angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation and Quantification of Angiogenesis Activity of Terminalia Bellirica Roxb, by Mice Sponge Implantation Method

Prabhu

Chidambaranathan

Gopal³

2012

Journal of Young Pharmacists

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Angiogenesis represents an excellent therapeutic target for the treatment of cardiovascular diseases. It is a potent physiological process that underlies the natural manner in which our bodies respond to a diminution of blood supply to vital organs, namely the production of new collateral vessels to overcome the ischemic state. This present study is aimed to evaluate and quantify the Angiogenic potential of Terminalia bellirica Roxb, by in vivo mice sponge implantation assay. Here, gelatin sponge with or without Ethanolic extract of Terminalia bellirica leaf (EETB - 0.3 mg and 0.5 mg, respectively) were subcutaneously injected into Swiss albino mice, and 14 days later, the implanted sponges was excised and histologically examined. The stained section showed that sponge containing EETB had produced more vessels in gels than sponges alone. The new vessels were abundantly filled with intact Red blood corpuscles (RBCs), which indicate the formation of a functional vasculature inside the sponges and blood circulation in newly formed vessels by angiogenesis which is induced by EETB. It also measured that the hemoglobin content inside the sponges: Whereas, hemoglobin in control was nearly 0.3 μg, EETB cases the hemoglobin quantity was markedly enhanced to about 17 μg. Taken together, it demonstrated that Ethanolic extract of Terminalia bellirica leaf exhibited a profound angiogenic activity in vivo. The phytochemical screening and qualitative instrumental analysis of EETB reveals the presence of proteins and Phytosterols. The promising angiogenic potential may be due to the presence of the above chemical constituents. Further study is required to define more precisely the molecular mechanisms by which Ethanolic extract of Terminalia bellirica leaf modulates endothelial cell function and gene expression, as well as the pathological relevance of these findings.

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Vascular Gene Therapy

Cited by 12 publications

References 65 publications

AAV-Mediated Expression of AP-1-Neutralizing RNA Decoy Oligonucleotides Attenuates Transplant Vasculopathy in Mouse Aortic Allografts

AAV-Mediated Expression of AP-1-Neutralizing RNA Decoy Oligonucleotides Attenuates Transplant Vasculopathy in Mouse Aortic Allografts

Genetics and Gene Manipulation Therapy of Premature Coronary Artery Disease

Evaluation and Quantification of Angiogenesis Activity of Terminalia Bellirica Roxb, by Mice Sponge Implantation Method

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