Human gene therapy is a medical approach that treats or prevents disease by modifying the expression of a gene or by altering the biological properties of living cells, allowing doctors to treat a disorder without requiring drugs or surgery. Gene therapy can be administered either ex vivo or in vivo. In ex vivo gene therapy, cells are removed from the body, altered, and reinserted, whereas in vivo gene therapy involves inserting new genes directly into the body.
Gene therapy was first studied in the 1960s, when several ways were being explored to introduce new genetic functions to mammalian cells. A virus, scientists hypothesised, could potentially be utilised as a vector to carry new genes into cells. The procedure was first used successfully in 1990 to treat a four-year-old girl born with a hereditary disease - severe combined immunodeficiency (SCID). Despite initial challenges, gene therapy has recently proven effective in treating a variety of diseases, including cancer, retinal problems, and hereditary abnormalities. Several techniques for delivery have been investigated over time, with the goal of delivering a gene that causes the expression or suppression of a protein. As of 2014, gene editing methods entail extracting cells from patients, modifying a chromosome, and then returning the transformed cells to the patients. Gene editing is a potential method for altering the human genome in order to treat hereditary illnesses, viral diseases, and cancer. These techniques are currently being explored in clinical trials with engineered zinc finger nucleases (gene-targeting tools) as of 2020.
Gene therapies can work in a number of ways:
replacing defective or damaged genes with healthy copies of the gene.
introducing a new or modified gene into the body to help treat a disease.
turning off disease-causing genes so that they no longer promote disease.
turning on beneficial genes that help prevent or inhibit the disease.
making diseased cells more visible to the immune system so that it can recognize the cells that are a threat.
Genes cannot be directly inserted into cells - they must be introduced using a vector. The most commonly used vectors are viruses, because of their natural ability to recognise certain cells and deliver genetic material into cells. The viruses are modified so that they cannot reproduce, and the disease-causing genes are removed and replaced with genes that cure the disease. The altered virus is mixed with cells harvested from the patient, making them genetically altered - these altered cells now have therapeutic abilities (e.g. can produce a desired protein), and are then injected back into the body. Some viruses, such as retroviruses, integrate their genetic material (including the new gene) into a human cell chromosome. Other viruses, such as adenoviruses, insert their DNA into the cell nucleus but do not integrate the DNA into a chromosome. Bacterial vectors can also be used by modifying them to prevent disease, and genetically engineering the plasmid DNA inside to carry therapeutic genes into human cells.
The use of gene therapy is currently authorised for a number of uncommon illnesses and cancers, such as melanoma, a type of skin cancer, spinal muscular atrophy, a genetic muscle condition, and Leber congenital amaurosis, a rare eye disorder. Human clinical trials of gene therapy have also shown some success in curing some disorders, including severe combination immune failure, haemophilia, blindness caused by retinitis pigmentosa and leukaemia. There are now numerous preclinical and clinical gene therapy studies being conducted for rare illnesses. Certain inherited diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency, beta thalassemia, and sickle cell disease may one day be prevented, treated, or even cured with the help of genetic therapy. It may also be used to treat malignancies or infections such as HIV. The UK government is supporting new gene and cell therapies that treat diseases by using living cells or genetic material like DNA, and the NHS stated that “The investment in this new centre will continue to develop this area of research and help provide patients the best possible care."
Due to the potential risks connected with gene therapies and the regulatory challenges that slow development, patients in high-income countries may still find access to gene therapy challenging. However, the outlook for people in low and middle income countries is dismal; as reported by the Institute for Clinical and Economic Review, the average cost of a gene treatment is between $1 million and $2 million per dose. Therefore, despite the huge advancements that gene therapy has already had, and will bring to the future of medicine, the huge production and research costs associated with such therapies can restrict access to a large extent.
In conclusion, gene therapy has made prodigious advancements over time, and the valuable possibilities that lie ahead provide a promising future for the field of medicine. Although the complexity of the innovation and vast expenses required may mean the progress is not smooth and the access is restricted, as technology further develops, these obstacles could be overcome, helping improve lives for thousands.