Delivery and Expression of Fluid Shear Stress-Inducible Promoters to the Vessel Wall: Applications for Cardiovascular Gene Therapy

Houston, Parul; White, Brian; Campbell, Callum J.; Braddock, Martin

doi:10.1089/10430349950016429

Cited by 36 publications

(35 citation statements)

References 79 publications

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“…This can be achieved by designing promoters that can be activated by orally administered drugs such as doxycyclin 101 or, alternatively, with the use of a promoter element responsive to physiological stimuli such as hypoxia 44,102 or shear stress. 103 Combining these approaches with tissue-specific promoters such as the endothelium-specific Tie-2 and smooth muscle cell-specific SM22␣ allows spatial control of the transgene expression in combination with temporal control. Although the development of the regulatable systems poses substantial challenges, it is imperative to develop safer and more specific gene therapy vectors for clinical use.…”

Section: Development Of Regulatable Vector Systemsmentioning

confidence: 99%

Antioxidant Gene Therapy for Cardiovascular Disease

et al. 2008

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Abstract-Excessive production of reactive oxygen species has been implicated to play an important role in a number of cardiovascular pathologies, including hypertension, atherosclerosis, myocardial infarction, ischemia/reperfusion injury, and restenosis after angioplasty or venous bypass grafting. The formation of reactive oxygen species is balanced out by antioxidant defenses, and augmenting this defense by antioxidant therapies could therefore provide a potential means to treat conditions in which the formation of reactive oxygen species exceeds the capability of natural protective mechanisms. In this review, we summarize the studies in which antioxidant gene therapy has been used successfully to treat cardiovascular diseases. We also discuss the current limitations of antioxidant gene therapy and envision future therapeutic targets and methodological approaches for an improved outcome. (Circulation. 2008;117:2142-2150.)

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Section: Development Of Regulatable Vector Systemsmentioning

confidence: 99%

Antioxidant Gene Therapy for Cardiovascular Disease

et al. 2008

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“…Many groups have utilised HREs to generate synthetic hypoxia-inducible promoter constructs. Houston et al [Houston et al, 1999] similarly developed shear-stress inducible promoter cassettes for application in cardiovascular gene therapy by the incorporation of shearstress response elements (see 'rational design').…”

Section: Stimulus-inducible Systemsmentioning

confidence: 99%

“…Several artificial promoters were isolated whose transcriptional potencies greatly exceeded those of some natural myogenic and viral gene promoters. Houston et al [Houston et al, 1999] used a similar but much smaller-scale approach to construct synthetic shear stressinducible promoters for cardiovascular applications, evaluating only thirteen plasmid constructs. In this study they evaluated the combination and spacing of a group of several common transcription binding sites, including Sp1, NF-kB and Ap1, in conjunction with a shear-stress response element (SSRE) to generate an inducible promoter construct that functioned from a plasmid vector delivered locally in vivo.…”

Section: Rational Design Of Promotersmentioning

confidence: 99%

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

Papadakis

Nicklin²,

Baker³

et al. 2004

CGT

146

121

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It has become apparent that the clinical success anticipated in the field of gene therapy has been limited by progress in several of the fundamental areas of genetics, molecular and cellular biology relevant to its application. Whilst a great deal of effort has been made in the evaluation of transgenes, it is only more recently with the advance of vector systems that attention has begun to be focused upon the means and control of transgene expression. Until recently, the majority of constructs have employed ubiquitous viral promoters to drive expression from simple gene expression cassettes using viral promoters and lacking introns, 3' untranslated regions (UTRs), locus control regions (LCR's), matrix attachment regions (MAR's) and other such genetic components. It has consequently emerged that these elements may have a key role in determining the levels and longevity of gene expression attainable in vivo, irrespective of the vector system utilised. The majority of gene therapy applications would also benefit from the specific optimisation of 'tailormade' expression cassettes to optimise their therapeutic efficacy. In conjunction with modification of vector tropism and strategies to limit their immunogenicity, this should create vectors suitable for the clinical application of gene therapy. This review aims to highlight some of the principle considerations of gene expression in vivo, and the means by which it may most effectively be achieved, whether this is via the minimal modification of an existing eukaryotic promoter or by the more extensive design of a novel promoter and associated elements.

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“…The addition of flow to a static system also inherently adds fluid shear stress. The addition of fluid shear stress augments mass and heat transport 5,6,17 and modulates cellular activity, [14][15][16]18,19 but the exact mechanisms through which it functions are incompletely known. The physiochemical factors that govern gene transfer for retroviral methods have been extensively considered.…”

Section: Introductionmentioning

confidence: 99%

Convective flow increases lipoplex delivery rate to in vitro cellular monolayers

Harris

Giorgio

2005

Gene Ther

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The mass transport characteristics of cationic, nonviral liposome-DNA plasmid complexes (lipoplexes) were evaluated over a range of fluid shear stresses. The typical case of stagnant flow transfection was expanded to include controlled fluid convection provided by constant flow through a parallel plate flow chamber. Equations describing the transport of lipoplex by sedimentation and convection were derived from theory and solved numerically. Instantaneous lipoplex delivery rate and total lipoplex surface delivery during a 72-h transfection were estimated for two shear stress levels and for static conditions. Theory predicted that lipoplex is delivered to the cell surface more than 12-to 19-fold faster through the addition of convection, at least for physiologic shear stresses of 2.3-9.7 dyn/cm 2 , respectively. These calculations were tested experimentally using a cell line (ECV-304) transfected with fluorescently labeled plasmid DNA formulated into a lipoplex. Transfections were conducted during cellular exposure to the same known, uniform levels of fluid shear stress presumed in theoretical calculations. Lipoplex delivery was increased by more than nine-fold at 2.3 dyn/cm 2 compared to the static case as assessed by flow cytometric measurement. Lipoplex delivery was modestly reduced at the highest fluid shear stress, to six-fold of the static case, consistent with the disruption of lipoplex-cell binding mediated by hydrodynamic forces. The complicated relationship between fluid convection and lipoplex delivery has important implications for nonviral gene therapy. Gene Therapy (2005) 12, 512-520.

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Delivery and Expression of Fluid Shear Stress-Inducible Promoters to the Vessel Wall: Applications for Cardiovascular Gene Therapy

Cited by 36 publications

References 79 publications

Antioxidant Gene Therapy for Cardiovascular Disease

Antioxidant Gene Therapy for Cardiovascular Disease

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

Convective flow increases lipoplex delivery rate to in vitro cellular monolayers

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