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What is Major transgene to achieve angiogenesis in cardiac muscles utilizes? and explain in detail?
Ans. A. VGEF. (Ref. H-17th/pg. 423)Harrison's medicine 17th/pg, 423.............."The major transgene used has been VEGF, attractive because of its specifici-ty for endothelial cells; other transgenes have included fibroblast growth factor (FGF) and hypoxia-inducible factor 1, ? subunit (HIF- 1?). "Gene transfer can be for:A. Genetic disease, B. Cancer, C. Cardiovascular diseases, D. OthersGENE TRANSFER FOR GENETIC DISEASE# most commonly involves transfer of the missing gene to a physiologically relevant target cell. However, other strategies are possible, including supplying a gene that achieves a similar biologic effect through an alternative pathway (e.g., factor Vila for hemophilia A);# supplying an antisense oligonucleotide to splice out a mutant exon if the sequence is not critical to the function of the protein (as has been done with the dystrophin gene in Duchenne muscu-lar dystrophy); or downregulating a harmful response through an siRNA.# Two distinct strategies are used to achieve long-term gene expression: one is to transduce stem cells with an integrating vector, so that all progeny cells will carry the donated gene; the other is to transduce long-lived cells, such as skeletal muscle or neural cells.GENE THERAPY STRATEGIES IN CANCER# Local/regional approaches: Suicide gene/prodrug, Suppressor oncogene, Oncolytic virus# Systemic response: Chemoprotection, Immunomodulation, Anti-angiogenesisTHERAPY FOR VASCULAR DISEASE# The third major category addressed by gene transfer studies is cardiovascular disease.# The most extensive experience has been in trials designed to increase blood flow to either skeletal (critical limb ischemia) or cardiac muscle (angina/myocardial ischemia).# The major transgene used has been VEGF, attractive because of its specificity for endothelial cells; other transgenes have included fibroblast growth factor (FGF) and hypoxia-inducible factor 1, ? subunit (HIF- 1?).# Continuing areas of investigation include choice of the optimal vector (adeno virs vs. plasmid), the optimal transgene (VEGF, HIF-1?, FGF, etc.), the optimal method of delivery in cardiac indications (intracoronary vs. direct myocardial), ideal objective end- points, and whether concurrent administration of cytokines to mobilize endothelial progenitor cells will augment the therapeutic effect.OTHER DISEASES# Other areas of interest include gene therapies for HIV and for neurodegenerative disorders.# Parkinson's disease.# In Alzheimer's disease, an ex vivo approach in which autologous fibroblasts are transduced with a retroviral vector expressing nerve growth factor, then reimplanted into the basal forebrain.