Genetic Engineering for Human Welfare

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.

  Content
» Cloned genes and production of chemicals

» Human peptide hormone genes


» Insulines


» Somatotropin


» Somatostatin


» b-endorphin

» Human interferon genes

» Genes for vaccines


» Vaccine for hepatitis-B virus


» Vaccines for Rabies virus


» Vaccines for poliovirus


» Vaccine for foot and mouth disease virus


» Vaccines for small pox virus


» Malaria vaccines


» DNA vaccines

» Genes associated with genetic diseases


» Phenylketonuria


» Urokinase


» Thalassaemia


» Hemophilia

» Enzyme engineering

» Commercial chemicals
» Prevention, diagnosis and cure of diseases

» Prevention of diseases

» Diagnosis of diseases


» Parasitic diseases


» Monoclonal antibodies


» Antenatal diagnosis

» Gene therapy


» Types of gene therapy


» Methods of gene therapy


» Success of gene therapy


» Potential of gene delivering system


» Future needs of gene therapy in India
» DNA profiling (fingerprinting)

» Methods of DNA profiling

» Application of DNA profiling


» Genetic databank


» Reuniting the lost children


» Solving disputed problems of parentage, identity of criminals, rapists, etc


» Immigrant dispute

» Hurdles of DNA profiling
» Animal and plant improvement

» Transgenic Farm Animals

» Crop Improvements


» Transgenic plants


» Nif gene transfer


» Phaseolin gene transfer


» Conversion of C3 plants to C4 plants


» Herbicide resistant plants


» Insect pest resistant plants


» Plant improvement through genetic transformation

» Crop Protection


» Use of antagonists


» Use of insecticides
» Abatement of pollution
Table 5.3. Clinical trials on gene therapy.  
Disease
Gene inserted
Cell types
Remark
ADA defficient SCID
ADA-gene
Peripheral T-lymphocytes and bone marrow cells
Repeated injections to be given
Duchenne's muscular dystrophy
Dystrophin gene
Myoblasts
Trials in USA
Haemophilia B
Factor IX
Autologous skin fibroblast
Trials in China
Cystis fibrosis
CFTR gene
-
Gene delivery to lung cells via liposomes