Recent Advances in Genetics: Gene Therapy
The insertion of genes into a diseased person for therapeutic purposes is a burgeoning area of genetics known as gene therapy. Its basic goal is to safely achieve the stable expression of a desired gene in the appropriate tissue (Reece et al. 2010, p. 424). The new gene can be used to replace a mutated gene, making this technique particularly effective in treating monogenetic diseases.
There are two primary types of gene therapy. The “ex vivo” technique involves surgical removal of cells from the affected tissue area followed by an injection of non-mutated DNA into the cells and letting them replicate (Sheridan 2011). The new tissues are then transferred back into the affected anatomy of the patient. Bone marrow cells are ideal for this procedure because they contain the stem cells that give rise to all blood cells that travel throughout the body (Reece et al 2012, p. 424). A drawback of this surgery is that it is extremely painful for the patient and two separate operations are required; one to extract the marrow and another to replace it. This image depicts ex vivo gene therapy:
In the second, more widely used gene therapy technique, genetically modified viral vectors are the main conduit for inserting genes into human cells. Scientists use this “in vivo” technique by exploiting viruses’ method of encapsulating then inserting their genes to host cells pathogenically. The below image illustrates this process:
To ensure the viral vectors do not manifest in a human host, they are pared down to a fraction of their genomes. This serves the dual purposes of expressing the new gene more robustly, and reducing the risk of an immune response to a viral antigen (Sheridan 2011). An example of in vivo gene therapy in practise is at Diamyd Medical in Stockholm, which is currently using a herpes simplex virus (HSV) in a gene therapy approach for pain (Sheridan 2011). This virus’ tropism for nerve tissue makes it particularly effective for targeted pain relief.
A wide variety of genes are being subject to gene therapy. Examples include a gene for the treatment of cystic fibrosis (a gene called CFTR that regulates chloride); the AC6 gene which increases the ability of the heart to contract and may prevent heart failure; genes for factors VIII and IX, deficiency of which is responsible for haemophilia A; genes known as E1A and P53 that cause cancer cells to undergo cell death or revert to normal; and VEGF, a gene that induces the growth of new blood vessels (angiogenesis) that are affected in blood vessel disease.
As scientists collate greater understanding of gene interactions, vector types and DNA control elements, gene therapy remains a rapidly evolving aspect of genetics. Currently, more advancements are still required regarding treatment of multifactorial diseases such as arthritis and heart disease, that involve two or more gene mutations. Research is also being conducted into the effects of foreign gene insertion on other necessary cell functions, and into methods of regulating the activity of the transferred gene to ensure the recipient cells make correct amounts of the gene product (Reece et al. 2012, p.425). Ethical questions such as the moral ambiguity of gene tampering and the possibility of epigenetics will also be major issues in the future of gene therapy.