Gene Therapy for Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 221

has been injected into patients with coronary artery disease. A placebo-controlled
clinical trial has assessed the safety and effects of combined treatment with the
plasmid VEGF-A165 and granulocyte-colony stimulating factor (G-CSF) mobili-
zation of bone marrow stem cells in patients with severe chronic ischemic heart
disease (Ripa et al. 2006 ). It was concluded that intramyocardial VEGF-A165 gene
transfer followed by bone marrow stem cell mobilization with G-CSF was safe.
However, a significant increase in circulating stem cells did not lead to improved
myocardial perfusion or clinical effects suggesting a neutral effect of the treatment.
To improve homing of stem cells, higher doses of VEGF-A165 and/or use of SDF-1
transfer might be considered.
Catheter-Based Systems for Vector Delivery
Catheter-based systems for vector delivery are shown in Table 8.2 along with their
advantages and disadvantages.
Ultrasound Microbubbles for Cardiovascular Gene Delivery
Ultrasound-targeted microbubble destruction can be used to deliver adenoviral or
plasmid DNA to the myocardium. This technique holds great promise in applying the
rapidly expanding repertoire of gene therapies being developed for cardiac disease.
Encapsulated gas microbubbles are well known as ultrasound contrast agents for
medical ultrasound imaging. They can also be used as drug/gene carriers. The
microbubbles as drug/gene carriers have an average size less than that of red blood
cells, that is, they are capable of penetrating even into the small blood capillaries
and releasing drug and genes under the action of ultrasound field. The application
of ultrasound and microbubbles to targeted drug and gene delivery has been the
subject of intense experimental research. Under exposure of sufficiently high-
amplitude ultrasound, these targeted microbubbles would rupture, spilling drugs or
genes, which are contained in the encapsulating layer, to targeted cells or tissues.
Recently, targeting ligands are attached to the surface of the microbubbles (i.e.,
targeted-microbubbles), which have been widely used in cardiovascular system
(Liu et al. 2006 ). Novel targeted ultrasonic contrast agents or microbubbles have
potential applications in cardiovascular gene therapy.
Vectors for Cardiovascular Gene Therapy
Both viral and nonviral vectors have been used for gene transfer to the cardiovas-
cular system. Nonviral vectors consist mainly of DNA plasmids. Retroviral vectors
have limited gene transfer efficacy because of low number of proliferating cells in
the cardiovascular system.