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  Section: General Biotechnology / Genes & Genetic Engineering
 
 
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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

 

 
     
 
 
     



     
 
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