Gene therapy is the use of DNA as a pharmaceutical agent to treat disease. It derives its name from the idea that DNA can be used to supplement or alter genes within an individual's cells as a therapy to treat disease. The most common form of gene therapy involves using DNA that encodes a functional, therapeutic gene to replace a mutated gene. Other forms involve directly correcting a mutation, or using DNA that encodes a therapeutic protein drug (rather than a natural human gene) to provide treatment. In gene therapy, DNA that encodes a therapeutic protein is packaged within a "vector", which is used to get the DNA inside cells within the body. Once inside, the DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patient's disease.

Gene therapy was first conceptualized in 1972, with the authors urging caution before commencing gene therapy studies in humans. The first FDA-approved gene therapy experiment in the United States occurred in 1990, when Ashanti DeSilva was treated for ADA-SCID.[1] Since then, over 1,700 clinical trials have been conducted using a number of techniques for gene therapy.[2]

Although early clinical failures led many to dismiss gene therapy as over-hyped, clinical successes since 2006 have bolstered new optimism in the promise of gene therapy. These include successful treatment of patients with the retinal disease Leber's congenital amaurosis,[3][4][5][6]X-linked SCID,[7] ADA-SCID,[8][9]adrenoleukodystrophy,[10]chronic lymphocytic leukemia (CLL),[11]acute lymphocytic leukemia (ALL),[12]multiple myeloma,[13]haemophilia[9] and Parkinson's disease.[14] These recent clinical successes have led to a renewed interest in gene therapy, with several articles in scientific and popular publications calling for continued investment in the field.[15][16]

In 2012, Glybera became the first gene therapy treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[17][18]

Scientists have taken the logical step of trying to introduce genes directly into human cells, focusing on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. However, this has proven more difficult than genetically modifying bacteria, primarily because of the problems involved in carrying large sections of DNA and delivering them to the correct site on the gene. Today, most gene therapy studies are aimed at cancer and hereditary diseases linked to a genetic defect. Antisense therapy is not strictly a form of gene therapy, but is a related, genetically mediated therapy.

The most common form of genetic engineering involves the insertion of a functional gene at an unspecified location in the host genome. This is accomplished by isolating and copying the gene of interest, generating a construct containing all the genetic elements for correct expression, and then inserting this construct into a random location in the host organism. Other forms of genetic engineering include gene targeting and knocking out specific genes via engineered nucleases such as zinc finger nucleases, engineered I-CreI homing endonucleases, or nucleases generated from TAL effectors. An example of gene-knockout mediated gene therapy is the knockout of the human CCR5 gene in T-cells to control HIV infection.[19] This approach is currently being used in several human clinical trials.[20]

Gene therapy may be classified into the two following types:

In somatic gene therapy, the therapeutic genes are transferred into the somatic cells (non sex-cells), or body, of a patient. Any modifications and effects will be restricted to the individual patient only, and will not be inherited by the patient's offspring or later generations. Somatic gene therapy represents the mainstream line of current basic and clinical research, where the therapeutic DNA transgene (either integrated in the genome or as an external episome or plasmid) is used to treat a disease in an individual.

In germ line gene therapy, germ cells (sperm or eggs) are modified by the introduction of functional genes, which are integrated into their genomes. Germ cells will combine to form a zygote which will divide to produce all the other cells in an organism and therefore if a germ cell is genetically modified then all the cells in the organism will contain the modified gene. This would allow the therapy to be heritable and passed on to later generations. Although this should, in theory, be highly effective in counteracting genetic disorders and hereditary diseases, some jurisdictions, including Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[21] prohibit this for application in human beings, at least for the present, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[21] and higher risk than somatic gene therapy (e.g. using non-integrative vectors).[22] The USA has no federal legislation specifically addressing human germ-line or somatic genetic modification (beyond the usual FDA testing regulations for therapies in general).[21]

Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by a number of methods. The two major classes of methods are those that use recombinant viruses (sometimes called biological nanoparticles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods).

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Gene therapy - Wikipedia, the free encyclopedia