Biomedical Engineering Reference
In-Depth Information
12
Gene Therapy Strategies:
Constructing an AAV
Trojan Horse
M. Ian Phillips
1
, Edilamar M. de Oliveira
2
, Leping Shen
1
,
Yao Liang Tang
1
and Keping Qian
1
1
Keck Graduate Institute, Claremont University Colleges, Claremont, California, USA
2
Laboratory of Biochemistry, School of Physical Education and Sport,
Sao Paulo University, Sao Paulo, Brazil
12.1 Introduction
There are many gene therapy strategies for a variety of diseases that could be treatable or
even curable by gene therapy. However, success has been limited. This reflects the state
of the field which is at various stages, and the limitation of tools. In theory, gene therapy
is very obvious: if a disease is monogenetic and due to a missing gene, then it should be
possible, if not simple, to provide the missing gene by inserting it into the chromosomal
position to which it belongs. The problem has been how to deliver the gene safely and
effectively.
Even if the disease is multigenetic, we know from drug therapy that manipulating a
specific gene or blocking a gene product can control the disease. For example, hypertension
undoubtedly involves multiple genes. But there are successful drugs to control high blood
pressure that inhibit specific gene products such angiotensin type 1 receptors, angiotensin
converting enzyme or renin. Therefore, even in cases of multigenetic diseases, inhibition of
a single gene delivered to cells could be an effective gene therapy.
To deliver DNA to replace genes or inhibitors of gene expression, researchers have
favored the Trojan horse approach with viral vectors. In the ancient story of Homer, the
Greeks, having besieged the city of Troy for 10 years, apparently gave up and sailed away.
