Gene Therapy Treatment

Gene Augmentation Therapy (GAT)

• Gene augmentation therapy (GAT), where DNA is added to the genome inorder to replace a missing gene product.
• Gene targeting to correct mutant alleles.
• Gene inhibition therapy, using antisense RNA expression or expression of intracellular antibodies to treat diseases.
• Targeted ablation of specific cells.
• Somatic cells can only be used as Therapeutic gene transfer generates transgenic human cell clones.
• In transient gene therapy oligonucleotides can be used which can distrupt gene expression at many levels but does not cause permanent genetic changes.
  
  Gene augmentation therapy for recessive diseases:
  
• Gene marking is the first human genetic engineering experiment to demonstrate that an exogenous gene could be safely transferred into a patient and that this gene could subsequently be detected in cells removed from the patients.
• Tumor infiltrating lymphocytes (kills tumor cells) were isolated from patients with advanced cancer. The cells were then genetically marked with a neomycin resistance gene and injected back into the same patient.
• Gene augmentation therapies are being undergone for a small number of recessive single gene diseases.
• Cystic fibrosis (disorder that affects lungs, liver and pancreas).
  The disease is caused by loss of cAMP -regulated membrane spanning chloride channel, which results in an electrolyte imbalance and accumulation of   mucus leading respiratory failure. Cystic fibrosis is a recessive disorder which can be altered by introducing a functional copy of the gene.
  
  Gene augmentation therapy for cancer:
  
• Different Gene therapy strategies are under study for cancer treatment.
• Tumor infiltrating leucocytes were transformed with a gene for TNF in addition to neomycin resistance gene with the aim of improving efficiency of these cells to kill tumors by increasing the amount of TNF they secrete.
• Transform the tumor cells themselves, making them more susceptible to immune system through expression of cytomines or foreign antigen.
• Transform Fibroblasts, which are easier to grow in culture and co-inject these together with tumor cells to provoke an immune response against the tumor.
• Oncogenes (cancer genes) can be targeted using antisense technology either with antisense transgenes, oligonucleotides or ribozyme.
• Cancers occurring due to loss of Tumor suppressor genes function can be altered by delivering a functional copy of  the appropriate gene delivered into affected cells.
• Pro-drug activation therapy involves activation of a particular enzyme specifically in cancer cells, which converts a non-toxic pro-drug into toxic product, so killing the cancer cells, which can be achieved by driving the   expression of so called "suicide gene" selectively in cancer cells.
• Use of Transcriptional regulatory elements that are active only in cancer cells.