Somatic cell gene therapy involves the transfer of gene to a diseased somatic cell either within the body or outside the body with the help of a viral or non viral gene therapy vector.
Ex vivo is any procedure accomplished outside. In gene therapy clinical trials cells are modified in a variety of ways to correct the gene. In ex vivo cells are modified outside the patient's body and the corrected version is transplanted back in to the patient. The cells are treated with either a viral or non viral gene therapy vector carrying the corrected copy of the gene.
Opposite of ex vivo is what we call in vivo where cells are treated inside the patient's body. The corrected copy of the genes is transferred into the body of the patient. The cells may be treated either with a viral or non viral vector carrying the corrected copy of the gene. If the patient is weak or the cell cannot be extracted out from the body, the gene is introduced directly into the body.
Gene therapy done in a restricted area or to a particular site is called in-situ . In situ gene therapy requires the vector to be placed directly into the affected tissues. In vivo gene therapy involves injecting the vector into the blood stream. The vector then must find the target tissue and deliver the therapeutic genes.
7.1 In situ gene therapy
In situ gene therapy comprises transfer of corrected copy of the gene into the targeted organ or tissue. The major concern of current time gene therapy protocol is the lack of efficient transduction of the targeted organ. The method is effectively used against cystic fibrosis, a disease of airway epithelium (discussed in later chapters). The method is also explored for cancer gene therapy where the viral vector is engineered to contain the herpes simplex virus thymidine kinase gene. After injection of the viral vector the patient is treated with a prodrug such as Ganciclovir, which causes 75% reduction in the tumor cell population.
7.2 In vivo gene therapy
Delivery of corrected copy of the gene systemically through injection is a highly efficient way to transfer a transgene to the patient's body. The major problem of in vivo method is its inefficient targeting. The transgene delivered into the body by means of viral or non viral vector also evokes the immune response. The immune response against the vector leads to its clearance and only transient expression of transgene. The neutralizing antibody does not allow the second injection of the vector. Reducing the neutralizing antibody is the current area of research in order to improve the delivery of gene therapy vector. All gene therapy delivery protocols require the transgene to cross the plasma membrane and enter inside the nucleus. The major obstacle is still to deliver the transgene effectively to the intracellular compartment. Many modifications have been suggested into the viral vectors and also non viral vectors to target the gene to the tissue. VP22, a protein of herpes simplex virus has a property to spread from one cell to the other, and this property has been successfully implemented in designing the vectors.