الفهرس 
WHAT’S GENEOnly 14 pages are availabe for public view
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Abstract
The complete genetic makeup of an individual is referred to their genome. Thus, in human cells the genome is composed of 23 pairs of chromosomes within the nucleus, each chromosomes containing a single, linear, double helical strands of DNA. The humane genome contains approximately 3 billions base pairs, and is thought to contain about 30 thousands different genes, most of which encode polypeptides. A small minority of genes encode RNA molecules. Gene is thought to be a segment of DNA molecule possessing a code for amino acid sequence of a polypeptide chain. This model however appears to be inadequate to elucidate precise mechanism of gene operation. There are about 50 to 100 thousand DNA sequences which code for RNA or protein products in man. These are called structural genes. On analysis of a structural gene, which reveals coding sequence called ”exons” which are interrupted by non coding sequences called ”introns”. ”Introns” are initially transcribed but are not represented in mature (mRNA) or in the final protein product. The gene also possesses extensive ”flanking regions”. They are important in regulation and the ”start” and ”stop” signals. Molecular ”treatment” requires, the molecular manipulation or alteration of a designated ”target” population of cells. Essentially, this change can be effected in one of two ways: by ex-vivo modification, with the material being re-introduced into the body after modification, or by in-vivo modification, done in situ. Whatever approach is adopted, the treatment will probably involve one of the following: gene replacement, gene addition, and gene control. Gene and their products can be delivered to a target tissue using either an ex-vivo or an in-vivo approach. Both approaches carry several advantages and drawbacks. Ex-vivo techniques rely on the isolation and cultivation of selected cells, their transfection in vitro and subsequent transplantation to a host, usually in an autologous manner. It is more laborious and expensive than in vivo gene transfer techniques in which genes are introduced directly to the target tissue bypassing the need for cell culture. In vivo methodologies can utilize some of the same vectors and transfection systems commonly used ex-vivo. New genes can be introduced into cells using either virus common viral vectors for gene therapy include: retroviral vectors, adenoviral vectors, adeno-associated viral vectors and herpes simplex viral (HSV) vectors. Chemical or physical methods: Electroporation, Cationic liposomes, Micro-seeding, Particle-mediated gene transfer, and naked DNA Advantage in techniques have resulted in practical application of gene therapy, which is becoming applicable for the treatment of human diseases. This review outlines the advantages and disadvantages of the techniques. Examples of research efforts in the treatment of diseases of relevance to the surgeon (cardiovascular diseases, cancer, wound healing, fracture repair, and in organ transplantation Plastic surgeons may soon see significant improvements in patient resulting using gene therapy that enhance tissue growth or repair, particularly in repair of skin, nerve, muscle, blood vessels, and cartilages. Skin is a good candidate for gene therapy not only because of its obvious accessibility, but also for its capacity for regeneration and abundant vascularity. As such, various growth factors and methods of gene transfer have been used in skin research: Epidermal growth factor (EGF), Insulin-like growth factor I (IGF-I) also mediate keratinocytes proliferation and migration through a paracrine mechanism, transforming growth factor B (TGF-B),and platelets derived growth factor B (PDGF-B). Gene therapy for ligaments that could help healing tissue achieve strength similar to normal ligaments would be an invaluable clinical tool through either adenovirus transmission of LacZ gene, haemaglutinin virus of Japan-liposome complex, direct injection of PDGF-B or antisense oligonucleotide therapy. Gene therapy that targets blood vessels is the most applicable to the field of plastic surgery when it focuses on one of two major processes: (1)Promoting blood vessels growth, or (2) Preventing graft failure. Three well known angiogenic factors are: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and nitric oxide.
Antisense oligonucleotides have been successful at preventing restenosis by suppressing smooth muscle cell intimal accumulation. The neural regenerative process is partly controlled by mediators termed ”neurotrophic factors”. Recently, researches have used gene delivery of neurotrophic factors to enhance nerve regeneration.
Neurotrophic factors are secreted from neuronal associated cells, such as Schwann cells, or targeted muscle and are taken up by neurons and transported in a retrograde manner to dorsal root ganglion or spinal motor neurons. A number of specific neurotrophic factors have been studied for gene therapy, but some of the best understood are brain derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), neurotrophin4/5 (NT4/5), and nerve growth factor (NGF).
Bone regeneration generally requires prolonged expression of cytokines, viral techniques are typically thought of as good vectors for this therapy. Mediators of bone development include, FGF, and members of TGF-B super family, such as TGF-B1 and bone morphogenic proteins (BMPs).
Gene therapy designed to improve cartilage repair can impact many fields of medicine: treatment of rheumatoid arthritis by transferring apoptotic proteins, or interleukin-1 receptors antagonists, or alleviate damaged osteoarthritic joint with the delivery of TGF-B or insulin-like growth factor.
Three different gene therapy for cancer treatment approaches: Immunotherapy, oncolytic virotherapy and gene transfer.
Immunotherapy uses genetically modified cells and viral particles to stimulate the immune system to destroy cancer cells. Recent clinical trials of second and third generation vaccines have shown encouraging results with a wide range of cancers, including lung cancer, pancreatic cancer, prostate cancer and malignant melanoma.
Oncolytic virotherapy, which uses viral particles that replicate within the cancer cell to cause cell death, is an emerging treatment modality that shows great promise, particularly with metastatic cancers.
Gene transfer is a new treatment modality that introduces new genes into a cancerous cell or the surrounding tissue to cause cell death or slow the growth of the cancer.
There are about 200 protocols for gene therapy that are approved worldwide. The trials are listed according to the disease or indication. Among the USA protocols, 17 concern AIDS, and 102deal with cancer. The cancer protocols are listed starting with cancer in general followed by various organs. Genetic disorders are listed and most of the protocols concern cystic fibrosis (13). Finally, 28 marker protocols are listed, all of which deal with cancer with the exception of one for AIDS.
Engineering of fetal tissue has a high potential for the treatment of acute and chronic wounds of the skin in humans A variety of sources, such as bone marrow, peripheral blood, umbilical cord blood, adipose tissue, skin and hair follicles, have been utilized to isolate stem cells to accelerate the healing response of acute and chronic wounds. Recently, the combination of gene and stem cell therapy has emerged as a promising approach for treatment of chronic and acute wounds.
Spinal cord injury (SCI) following trauma or secondary to skeletal instability is a terrible condition with no effective therapies available at present.It showed that the G-CSF receptor is up-regulated upon experimental SCI and that G-CSF improves functional outcome in a partial dissection model of SCI.