8-4.4 Meeting the challenges in gene therapy

Some issues that need to be addressed before gene therapy could be successful are:

1. Identifying the correct therapeutic gene to inhibit disease progression.
   
   
2. Identification of key target genes critical for the disease pathology and progression. Inhibition of a single target gene sometimes is not sufficient to inhibit the disease as there may be alternate pathways compensating the function.
   
   
3. Optimal trans-gene expression for suppressing the offending/target gene.
   
   For optimized trans-gene expression two important components are required: promoters and enhancers to determine the time duration of trans- gene expression in the target cell or tissue. There are two types of promoters: constitutive or inducible.
   
   The constitutive promoters can be either of viral origin (e.g. Cytomegalovirus) or tissue specific promoters, such as melanin for melanoma or the prostate specific antigen (PSA) for prostate cancer. Inducible promoters can be induced by inducers (small molecules or hormones) and leading to transient expression of the transgene.
   
   Enhancer sequences are inserted to upstream portions of the promoters to increase the trans - gene expression ability by 2-100 times. This is required in the case when the gene product needed in very high concentrations inside the target cell. The trans-gene expression duration will depend on the cell's requirements and nature of the product.
   
   
4. Delivery of therapeutic product to the target tissue at an efficacious dose:
   
   This depends upon the disease. In cancer cells, the duration of expression may need to last for only a short time up to 30 days. In contrast, genetic diseases may require long-term expression from months to years that may require highly effective transfection and integration of the gene.