The journal of gene medicine
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Previous studies have shown that TIMP-2 overexpression is a useful therapeutic tool for inhibiting tumor growth and invasion in animals. However, it has not been reported whether genetic manipulation for TIMP-2 overexpression can induce an inhibitory effect on spontaneous metastasis from the primary tumor site to other organs such as lungs or lymph nodes in an animal model. ⋯ Retrovirus-mediated TIMP-2 gene transfer into human breast cancer cells is able to down-regulate invasion and show that tumor-derived angiogenesis is reduced. In this model, retroviral-mediated transduction of TIMP-2 cDNA into a limited population of human tumor cells inhibits tumor growth and prevents distant pulmonary metastasis. These results indicate that it may not be necessary to deliver and express these genes in every single tumor cell as long as the level of expression in a limited number of transduced cells is sufficient to prevent the excessive breakdown of the extracellular matrix.
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The activity of synthetic antisense oligonucleotides (splicomers) designed to block pre-mRNA splicing at specific exons has been demonstrated in a number of model systems, including constitutively spliced exons in mouse dystrophin RNA. Splicomer reagents directed to Duchenne muscular dystrophy (DMD) RNAs might thus circumvent nonsense or frame-shifting mutations, leading to therapeutic expression of partially functional dystrophin, as occurs in the milder, allelic (Becker) form of the disease (BMD). ⋯ These results suggest that correctly designed splicomers may have direct therapeutic value in vivo, not only for DMD, but also for a range of other genetic disorders.
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Comparative Study
Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model.
Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) play important roles in vascular formation and maturation, suggesting that the combination of these two would be a promising therapy for ischemia. However, it remains unclear what the best schedule of administration of these cytokines might be. ⋯ The pre-administration of Ang1 followed by VEGF resulted in an improvement of hemodynamic status, an increased number of vessels covered with alpha-actin-positive mural cells, and prevention of VEGF-mediated edema. Thus, priming by Ang1 gene administration would be beneficial for therapeutic angiogenesis in VEGF gene therapy.