Gene transfer to the vascular system: Novel translational perspectives for vascular diseases

Remes, Anca; Basha, Dima Ibrahim; Frey, Norbert; Wagner, Andreas H.; Müller, Oliver

doi:10.1016/j.bcp.2020.114265

Cited by 8 publications

(6 citation statements)

References 113 publications

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“…Additionally, these approaches provide reduced immunogenicity, another major challenge that prevents AAV-based strategies from being translated into clinical practice [ 23 ]. An extensive summary of the most current delivery methods, modes of application, and possibilities to increase the vascular system’s transduction efficiency have been reviewed recently [ 24 , 25 ].…”

Section: Overview Of Gene Therapymentioning

confidence: 99%

“…Conventional techniques often use systemic viral vector administration. However, an injection into the blood lowers the local AAV concentration and hence the transduction efficiency, particularly within large vessels like the aorta [ 24 ]. Delivering vascular-specific AAV vectors by inserting endothelial-targeting peptides into capsid proteins might overcome this limitation [ 49 ].…”

Section: Transcription Factor Decoy-mediated Inhibition Of Aortic Ela...mentioning

confidence: 99%

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Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Kallenbach

Remes

Müller

et al. 2022

JCM

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Marfan syndrome (MFS) is one of the most common inherited disorders of connective tissue caused by mutations of the fibrillin-1 gene (FBN1). Vascular abnormalities, such as the enlargement of the aorta with the risk of life-threatening rupture are frequently observed. However, current treatment is limited and therapeutic options focus solely on symptomatic therapy. Gene therapy focuses on genetically modifying cells to produce a therapeutic effect and may be a promising treatment option for MFS. Here, we first provide an overview of the historical background and characterization of MFS. Subsequently, we summarise current gene therapy options and possible translational concepts for this inherited disorder that affects connective tissue.

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Section: Overview Of Gene Therapymentioning

confidence: 99%

Section: Transcription Factor Decoy-mediated Inhibition Of Aortic Ela...mentioning

confidence: 99%

Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Kallenbach

Remes

Müller

et al. 2022

JCM

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“…Delivery of this hydrogel to murine, ischemic hindlimbs resulted in superior recovery of blood perfusion as compared with a bolus injection of VEGF‐encoding plasmids. These results may be skeletal muscle specific as biomaterial‐delivered gene therapy has not been shown to be as successful in other tissues, such as those found in the vascular system 114,115 …”

Section: Release Of Bioactive Moleculesmentioning

confidence: 99%

“…These results may be skeletal muscle specific as biomaterial-delivered gene therapy has not been shown to be as successful in other tissues, such as those found in the vascular system. 114,115 As our knowledge of both biomaterials and gene delivery continues to develop, there is hope that the convergence of these two technologies will result in novel muscle regeneration therapies.…”

Section: Gene Therapymentioning

confidence: 99%

Promoting endogenous repair of skeletal muscle using regenerative biomaterials

Carleton

Sefton

2021

J Biomedical Materials Res

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Skeletal muscles normally have a remarkable ability to repair themselves; however, large muscle injuries and several myopathies diminish this ability leading to permanent loss of function. No clinical therapy yet exists that reliably restores muscle integrity and function following severe injury. Consequently, numerous tissue engineering techniques, both acellular and with cells, are being investigated to enhance muscle regeneration. Biomaterials are an essential part of these techniques as they can present physical and biochemical signals that augment the repair process. Successful tissue engineering strategies require regenerative biomaterials that either actively promote endogenous muscle repair or create an environment supportive of regeneration. This review will discuss several acellular biomaterial strategies for skeletal muscle regeneration with a focus on those under investigation in vivo. This includes materials that release bioactive molecules, biomimetic materials and immunomodulatory materials.

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“…Effective atheroprotective gene therapy, whether delivered via EC or other cells, requires expression cassettes that achieve high-level transgene expression 7 . In earlier work developing EC-targeted gene therapy for atherosclerosis, we showed that EC overexpression of apolipoprotein AI (APOAI)-using an expression cassette containing the cytomegalovirus (CMV) immediate early promoter-can slow or reverse atherosclerosis in hyperlipidemic rabbits [8][9][10] .…”

mentioning

confidence: 99%

Novel expression cassettes for increasing apolipoprotein AI transgene expression in vascular endothelial cells

Sethuraman

Dronadula

et al. 2022

Sci Rep

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Transduction of endothelial cells (EC) with a vector that expresses apolipoprotein A-I (APOAI) reduces atherosclerosis in arteries of fat-fed rabbits. However, the effects on atherosclerosis are partial and might be enhanced if APOAI expression could be increased. With a goal of developing an expression cassette that generates higher levels of APOAI mRNA in EC, we tested 4 strategies, largely in vitro: addition of 2 types of enhancers, addition of computationally identified EC-specific cis-regulatory modules (CRM), and insertion of the rabbit APOAI gene at the transcription start site (TSS) of sequences cloned from genes that are highly expressed in cultured EC. Addition of a shear stress-responsive enhancer did not increase APOAI expression. Addition of 2 copies of a Mef2c enhancer increased APOAI expression from a moderately active promoter/enhancer but decreased APOAI expression from a highly active promoter/enhancer. Of the 11 CRMs, 3 increased APOAI expression from a moderately active promoter (2–7-fold; P < 0.05); none increased expression from a highly active promoter/enhancer. Insertion of the APOAI gene into the TSS of highly expressed EC genes did not increase expression above levels obtained with a moderately active promoter/enhancer. New strategies are needed to further increase APOAI transgene expression in EC.

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Gene transfer to the vascular system: Novel translational perspectives for vascular diseases

Cited by 8 publications

References 113 publications

Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Promoting endogenous repair of skeletal muscle using regenerative biomaterials

Novel expression cassettes for increasing apolipoprotein AI transgene expression in vascular endothelial cells

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