INTRODUCTION
Somatic gene therapy is defined as the transfer of a heterologous gene with the purpose of correcting a genetic defect or providing a new therapeutic function to the target cell, and thus curing a disease or alleviating associated symptoms. The rationale of somatic gene therapy is the correction of diseases at the most fundamental level: the genetic code. Ideally, this goal should be achieved by correcting a defective gene in the human genome. However, correcting the actual genetic defect (i.e., a premature STOP codon in the coding sequence for a certain gene) is not possible because: (a) genetic tools to alter DNA of living cells in such a way are not available (b) often, genetic mutations in a specific gene are heterogeneous (see example for OTC deficiency below). At present, gene transfer technology may provide:
1. Expression of a functional copy of the gene of interest (this is only effective when the genetic defect is of recessive nature).
2. Addition of a new function by transferring an exogenous gene (Example: an antisense RNA against a virus).
3. Inhibition of the unfavorable action of a gene by introducing a counteracting gene (Example: delivery of anti-inflammatory mediators in rheumatoid arthritis).
Gene therapy is most commonly associated with genetic deficiencies. But the spectrum of potential applications of gene therapy goes well beyond that:
- Genetic deficiency
- Viral infection (Example: human immunodeficiency virus)
- Autoimmunity (example: rheumatoid arthritis)
- Cancer
- Diseases in which several genes and the environment interact, such as diabetes, coronary artery disease.
