Molecular Imaging in Gene Therapy

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.

Although early clinical failures led many to dismiss gene therapy as over-hyped, clinical successes in 2006–2013 have bolstered new optimism in the promise of gene therapy. These include successful treatment of patients with the retinal disease Leber's congenital amaurosis, X-linked SCID, ADA-SCID, adrenoleukodystrophy, chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), multiple myeloma and Parkinson's disease.  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.  In March 2013, Researchers at the Memorial Sloan-Kettering Cancer Center in New York, reported that three of five subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not.

Gene therapy may be classified into the two following types:

Somatic gene therapy

In somatic gene therapy, the therapeutic genes are transferred into the somatic cells, or body, of a patient/subject. 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.

Germ line gene therapy

In germ line gene therapy, germ cells, i.e., sperm or eggs, are modified by the introduction of functional genes, which are integrated into their genomes. 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, many jurisdictions prohibit this for application in human beings, at least for the present, for a variety of technical and ethical reasons.

Molecular imaging has emerged as a powerful way to assess the location, magnitude, and duration of transgene expression in a living subject. For several years, optical reporters such as green fluorescent protein (GFP) and other color variants have been used to monitor gene expression. Reporters for nuclear imaging have also been developed because the tracer amounts of radioactivity are highly quantitative and sensitive, and are directly applicable to clinical trials.


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