Success of gene therapy
The success of gene therapy depends on gene delivery mechanism as well as on the choice of target tissue. Rangarajan and Padmanaban (1996) have discussed different conditions leading to success of gene therapy:
(i) Cell types capable of dividing in vitro (e.g.
myeloblasts, hepatocytes, keratinocytes, endothelial cells, etc.) are amenable for in vitro
and in vivo
gene therapy, both the in vivo
methods are preferred for cell types such as neuronal cells.
(ii) The function of gene products also govern the selection of tissues, for example in case of haemophilia a gene can be delivered in any tissue provided the gene product is released into blood stream. In addition, in case of cystic fibrosis the gene should be delivered to specific cell types where introduction of correct gene is required.
(iii) Another attractive strategy for the treatment of several disorders is antisense gene transfer, for example in b-thalassemia, a-globin chains are accumulated in RBCs that result in their premature decay. Such types of destruction can be prevented by infection of K562 erythroleukemia cells with AAV expressing human a-globin gene in antisense orientation.
(iv) The potential of a gene delivery system is first found out in cultured cells or laboratory animals by using reporter genes (for luciferase, growth hormone, b-galactosidase, etc. For detailed discussion on reporter genes see Biotechnological Applications of Plant Cell, Tissues and Organ Cultures
). On the basis of result of these studies again pretrials are conducted in laboratory animals to test the level and duration of expression of the introduced genes. Finally clinical efficacy is evaluated in human patients. But before conducting clinical trials in humans permission is necessary from the Regulatory Agencies such as recombinant DNA Advisory Committee (RAC) and the Food and Drug Administration (FDA) in the USA, the Gene Therapy Advisory Committee (GTAC) in the UK, etc. In India also guidelines have been formulated (see Biotechnology and Biosafety, Intellectual Property Right (IPR) and Protection (IPP)).
Clinical trials on gene therapy are given in Table 5.3.
(v) Table 5.3. Clinical trials on gene therapy.
|ADA defficient SCID
||Peripheral T-lymphocytes and bone marrow cells
||Repeated injections to be given
|Duchenne's muscular dystrophy
||Trials in USA
||Autologous skin fibroblast
||Trials in China
||Gene delivery to lung cells via liposomes