Gene Therapy
A primary focus of medical science today is finding ways to treat life-threatening diseases of our time, including AIDS and cancer. But cures for these and other major diseases have proven largely elusive to scientists, despite millions of dollars in medical research. However, hope has arrived over the past few decades in the form of an innovative approach to disease treatment known as gene therapy. Gene therapy, which is the use of genetic material such as DNA to manipulate a patient’s cells, is showing great promise in clinical trials as the new horizon in modern medicine.
Theodore Friedmann and Richard Roblin first proposed the concept of gene therapy in 1972 in their co-authored article titled, “Gene therapy for human genetic disease?” They cited Stanfield Roger’s idea from 1970 that healthy DNA could be used to replace defective DNA in people with genetic disorders. Friedmann and Roblin built off of Rogers’ idea and made concrete suggestions for how healthy DNA could be used to either fix, replace or supplement a faulty gene so that it can function properly. Researchers quickly latched onto this concept, and the first gene therapy case was approved in the United States in September of 1990.
How gene therapy works is that DNA encoding a therapeutic gene is administered to a patient in a way that facilitates the DNA entering a dysfunctional cell and then allowing for the expression of a therapeutic protein. In most cases the encoded therapeutic gene is a natural human one, but in some cases a synthetic protein drug is encoded instead. The difficult part of this process is getting the unhealthy cell to accept the therapeutic gene. While methods that involve directly injecting the naked DNA into the recipient cell have shown some success, the far more commonly employed method is through the use of a vector—a DNA molecule that serves as a vehicle to artificially carry foreign genetic material into another cell.
The most common type of vector is an engineered virus. A virus is an efficient vector because viruses naturally invade cells and insert their genetic material into a cell’s genome as part of their replication cycle. But to use a virus as a vector, some of the virus’s DNA has to be removed and replaced with the therapeutic DNA. The virus’s larger structural sequence stays intact and serves as the “backbone” of the vector, which tricks the patient’s cells into allowing it to enter and insert the therapeutic gene. The types of viruses that can be used as vectors include HIV, adenoviruses, and herpes simplex viruses.
Gene therapy can further be categorised into somatic and germline therapy. In somatic gene therapy, the therapeutic DNA is transferred into the somatic, or non-sex cells, of a patient. This means that any modifications to the patient’s genes will not be passed onto the patient’s offspring, and thus the effects of the gene therapy are restricted to the patient only. On the other hand, germline gene therapy involves the introduction of the healthy genes into the sperm or eggs of the patient. This results in the modifications created by the functional DNA being integrated into the patient’s genomes and being inherited by their offspring. Germline gene therapy thus has more potential to effectively eradicate hereditary disorders, but due to certain risk factors at this juncture in the development of gene therapy, most countries currently prohibit germline gene therapy in humans.
The risk factors herein alluded to are part of a broader set of concerns about both the safety and long-term viability of gene therapy in humans. There are some general risks associated with the therapy that have yet to be resolved. One is the potential for a patient’s immune response to kick in when the foreign DNA is introduced and attack the invader. This has made it challenging for gene therapy to be repeated in patients. Another problem is with the use of viruses as vectors. Even when a virus is engineered, there is always the risk that the viral vector will recover its ability to cause disease once inside the patient. Viral vectors have also been associated with issues such as immune and inflammatory responses, toxicity to the patient’s tissues, and difficulties with gene control and targeting. These are just some of the many risks to a patient’s physical health that can occur with gene therapy.
However, despite these challenges, gene therapy has proven itself as a potential treatment model, having successfully cured patients with diseases such as chronic and acute lymphocytic leukemia, haemophilia, and Parkinson’s disease. Further, clinical trials have hinted at possible breakthroughs in the treatment of diabetes type I and retinitis pigmentosa, a leading cause of vision loss. These clinical successes paved the way for the approval of the first gene therapy for clinical use in either Europe or the United States in 2012. They also attracted the attention of investors, resulting in over $600 million in the United States alone being poured into gene therapy by private companies. With all of these resources and attention going into research, we will undoubtedly be seeing great advances in the field of gene therapy in the coming years.