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Tissue-specific targeting for cardiovascular gene transfer. Potential vectors and future challenges

Journal article
Authors Caroline Beck
Hidetaka Uramoto
Jan Borén
Levent Akyürek
Published in Current Gene Therapies
Volume 4
Issue 4
Pages 457-67
ISSN 1566-5232
Publication year 2004
Published at Wallenberg Laboratory
Institute of Anatomy and Cell Biology
Pages 457-67
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adenoviridae/genetics, Animals, Cardiovascular System/*metabolism, Endothelium, Vascular/metabolism, Gene Expression, Gene Therapy/*methods/trends, Gene Transfer Techniques, Genetic Engineering, *Genetic Vectors, Humans, Macrophages/metabolism, Muscle, Smooth, Vascular/metabolism, Organ Specificity, Promoter Regions (Genetics)
Subject categories Medical and Health Sciences

Abstract

The introduction of genes to cardiovascular cells in vivo remains the major challenge for current gene therapy modalities. However, recent developments in retargeting adenoviral vectors are promising to improve transduction efficiency in the cardiovascular cells. After systemic application, most adenoviral vectors are trapped by the liver, hampering delivery to target cardiovascular tissues. Furthermore, a majority of vectors for vascular gene transfer utilizes strong heterologous viral promoters, such as CMV. A potential side effect related to the use of such vectors is the systemic organ toxicity resulting from unrestricted transgene expression. These vectors have the additional problem of being frequently shut-down in vivo. Therefore, both retargeting adenoviral vectors and the use of tissue-specific promoter-driven vectors offer an enhanced safety profile by reducing ectopic expression in vital organs including the liver and lung. However, the limiting factor for the use of tissue-specific promoters is the low-level of expression compared with their viral counterparts. Both the development of efficient and strong vectors using cell-specific regulatory elements and the production of therapeutic proteins at sufficient levels is urgently needed to inhibit vasculoproliferative disorders. This review will focus on some of the recent achievements in vector development relevant to the delivery of vascular gene therapies targeted to the vascular endothelium, smooth muscle cells and macrophages during arterial remodelling.

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