Identification of disease genes and somatic gene therapy: an overview and prospects for the aged

Positional cloning strategies for identification of disease genes include genetic linkage analysis in disease families and identification of individuals in whom the disease is associated with a specific chromosomal anomaly. Once a genomic region likely to contain the disease gene has been identified, overlapping genomic clones are isolated and the candidate gene sought. Somatic gene therapy entails introduction of the cloned gene into somatic cells to either replace genetically defective functions or alter pathological disease processes. Transfer of the gene may be accomplished by either DNA- or viral-mediated methods into a variety of tissue targets. Once the success and reliability of ongoing gene therapy trials for various human diseases is established, it may then be considered in the prevention and treatment of chronic, disabling diseases such as Alzheimer's disease, Parkinson's disease, arthritis, and diabetes as well as intervention of immunosenescence, when the relevant genes have been cloned. Ethical considerations for gene therapy for aging are similar to those for gene therapy in general. In addition, the ethics of gene therapy for treating diseases versus intervention of the normal aging process must be considered.