Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 270

6

Applications of Gene Therapy

Mukesh Kumar, Ambikanandan Misra
Pharmacy Department, TIFAC - Centre of Relevance and Excellence in New
Drug Delivery Systems, The Maharaja Sayajirao University of Baroda,
PO Box 51, Kalabhavan, Vadodara 390 001, Gujarat, India

6.1 Gene Therapy

A number of common human diseases have underlying genetic causes, and pharma-
cological approaches often fall short of curing many of these diseases. Gene therapy
is defined as the correction of dysfunctional or deleted genes by supplying the lacking
component as a means to permanently treat or reverse such diseases [1] . Gene therapy
provides a unique approach that can be used in the treatment of both inherited and
acquired diseases. Researchers in gene therapy have used one of the ways for correct-
ing defective genes such as replacement of a nonfunctional gene with a normal gene,
or an abnormal gene with a normal gene, through homologous recombination; or for
repairing an abnormal gene through selective reverse mutation or selectively control-
ling expression of a defective gene [2,3] . In another type of application, the genes
may also be delivered as genetic vaccines to induce both cell-mediated and humoral
immune responses.
The fundamental principle underlining gene therapy is theoretically straightfor-
ward, but difficult to achieve in practice satisfactorily. The two essential components
of gene medicine are therapeutic gene coding for a protein along with its expression
regulatory component and the gene delivery system [4] . Many genes capable of cor-
recting diseased phenotypes have been identified, and it is now possible to produce
engineered DNA that carries a therapeutic gene in sufficient quantities for clinical tri-
als. The simplified schematic general process of gene therapy is shown in Fig. 6.1 .
Initially, the required desired gene (or DNA-containing gene) is complexed, com-
pacted, and packaged into a suitable vector, either viral or nonviral, to form the DNA-
vector system. This system or the DNA alone is introduced into the target cells, using
a physical, chemical, or biological method, where it gets dissociated to release the
DNA. The released DNA, with or without integrating to the host cell DNA, expresses
itself to produce protein, using the host cell machinery; this is followed by the thera-
peutic effect.

6.1.1 Approaches for Gene Therapy
Gene therapy is a relatively new technology that holds great promise for treating a
myriad of diseases in a unique manner. In genetic diseases, delivering the functional