INTRODUCTION TO GENE THERAPY

The cumulative research directed towards understanding the molecular
biology underlying all aspects of disease & development has yielded
a wealth of information. As gene products & their interactions with
the cellular environment have been characterised, so the possibility
of treating disease by using DNA as a drug has arisen. All proteins
are coded for by DNA, & diseases ultimately result from the
expression of one or more abberent proteins, e.g. an oncogene or
pathogen protein, or the lack of a functional form. In theory
therefore, all diseases could be treated by expression of the
appropriate protein in the effected cells. Conceptually the most
simple disease to treat would be a monogenic recessively inherited
disease, such as haemophilia , whereby the functional form of the
gene would be added to the cell restoring it to a normal phenotype.
However, research is underway to treat monogenic dominantly
inherited diseases such as hypercholesteroleamia , & acquired
genetic diseases such as cancers. Regulation of cellular
proliferation e.g. to prevent atherosclerosis following
angioplasty , or to promote of cellular repair following trauma to
the CNS & protection from infectious disease are also currently
being investigated.

Gene therapy potentially represents one of the most important
developments to occur in medicine, but before this can be realised
certain technical problems common to all methods of gene delivery
must be overcome. In order to modify a specific cell type or tissue,
the therapeutic gene must be efficiently delivered to the cell, in
such a way that the gene can be expressed at the appropriate level &
for a sufficient duration. Two broad approaches have been used to
deliver DNA to cells, namely viral vectors & non-viral vectors,
which have different advantages as regards efficiency, ease of
production & safety. This paper will review these methods & then
discuss the genetic strategies used to achieve prolonged tissue
specific expression of the therapeutic gene.