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Imagine a world where diseases are not just managed but cured at their roots. Sounds
questionable right? It is now actually possible with the development in the field of genetics!!
You all must have come across some words like occupational therapy, physiotherapy, psychotherapy, etc. But have you ever heard about gene therapy? Many of you might not have. Through this blog, I am going to explain what gene therapy actually is, how it works, and how this innovative technique has the potential to cure harmful diseases that cannot be treated with the help of medicine or surgery.
In simpler terms, we can say that gene therapy means altering the genes inside your body’s cells in an effort to treat or stop a disease. “Gene” is a segment of DNA that carries information from one generation to another and determines hereditary characteristics in an offspring. A faulty gene (wrong nucleotide sequence produced by mutations) does not work properly and hence causes several genetic diseases. So, gene therapy replaces this faulty gene with a correct gene and hence it either cures the disease or improves the body’s ability to fight that disease.
Gene therapy is a technique that modifies a person's genes to treat or cure the disease.
More than 30 years ago, visionary researchers coined the term "gene therapy," implying that for some conditions, primarily monogenic diseases, replacing the missing or mutated gene with the normal allele via gene addition could have long-lasting therapeutic effects on the patients and subsequently enhance their quality of life. For some illnesses, such as hemoglobinopathies, immunodeficiencies, and other monogenic disorders, this idea has just lately come to pass.
TYPES OF GENE THERAPY
There are two types of gene therapy based on the type of cell that is mutated:
● Somatic cell gene therapy - It is one of the safest methods of gene therapy. Here, the faulty gene present in somatic cells is replaced with the healthy ones. Now you might wonder what somatic cells are; These are nothing but the cells in the body other than germ cells i.e. sperm and ovum. But it should be noted that any positive effects of this therapy are restricted to that person only and won't get inherited by the next generation i.e. the child of the person will have the disease even if the person gets cured.
● Germline gene therapy - This process involves the introduction of healthy genes into the cells responsible for producing eggs or sperm. These introduced genes then are integrated into the genome. Do you know that it is better than somatic cell gene therapy as these modifications are hereditary i.e. they pass on to the next generation? In this case, unlike the previous one, both the parent and the child will be disease free.
DIFFERENT WAYS TO CURE DISEASES USING THIS TECHNIQUE
Gene therapy works by several different mechanisms:
1. Sometimes due to mutation, gene expression - (production of desired protein product) - gets altered so that the wrong protein is formed or very few molecules of that protein are formed. This is one of the basic causes of any genetic disease. So, by replacing this mutated gene with the help of gene therapy, the disease can be treated. For example, a gene called p53 prevents tumor growth. Many types of cancer are linked to the defects in this gene p53. Just imagine how awesome it would be if scientists are able to replace this mutated gene with a normal one! People will be able to live a cancer-free life!!
2. The disease can be cured by fixing the mutated gene. These mutated genes can be turned off(to stop the gene expression) or the healthy genes that have the ability to make proteins that will prevent the disease can be turned on(to increase the gene expression)
3. Sometimes, our immune system can't attack mutated cells as it is not able to recognize them as intruders. But scientists can use this gene therapy technique to make the immune system capable of identifying these cells.
Inserting a healthy gene into the cell is a widely used method. Let's look at the 3 basic steps involved in this:
i) Gene Identification: first we need to identify the faulty gene and then we need to find out the correct sequence of the gene.
ii) Duplication: The second step involves the duplication of the gene of interest which will be used for therapy.
iii) Inserting Duplicated Gene: Lastly the duplicated gene is inserted into the recipient cell.
Now you might wonder how we will insert this correct duplicated gene inside the cell.
● It is quite fascinating that other than the genome(DNA), the plasmid is also present inside bacteria. A plasmid is a circular DNA molecule that replicates independently inside bacteria. Earlier scientists found it useless but now they have found a way to utilize it to introduce the desired gene inside the host cell(mutated). In simple terms, a plasmid can act as a vector. It usually contains a gene for antibiotic resistance. Moreover, it is believed that this plasmid-mediated gene therapy method can be used to treat several cardiovascular diseases for which many clinical trials are still going on. For example, heart failure can be treated by delivering the plasmid, having desired genes (Elastin, SERCA2a, HGF, etc.) by giving an intramuscular injection. The host cells in this case are cardiomyocytes.
● It has been found that viruses too have an ability to deliver genetic material into the cells. This ability of viruses is now being used to insert healthy genes into the host cell. The most commonly used viral vectors are lentivirus and an oncogenic retrovirus called murine leukemia virus.
To explain it in simple terms, the desired gene in both plasmid DNA and viral DNA gets incorporated into the host DNA, at the time of replication, once it enters the host cell.
Scientists usually prefer the 1st method as it offers less potential hazard than viruses. And based on my knowledge I believe that 1st method is actually more reliable due to their easy propagation in large quantities and very little immunogenicity.
Currently, gene therapy exists predominantly in research labs although trials are being conducted to see if it will be successful in curing harmful diseases such as hemophilia, cystic fibrosis, muscular dystrophy, cancer, AIDS, etc. Scientists believe that this technique will be utilized efficiently in a few years as few trials have been successful. They believe that it needs new developments. Despite all these, there are few diseases that are solely treated by this method these days. Leber congenital amaurosis is a rare hereditary disease that causes blindness, however, there is presently FDA-approved genetic therapy for the disorder. The FDA has authorized CAR T-cell therapy for the treatment of blood malignancies that cause Diffuse large B-cell lymphoma (DLBCL) and acute Lymphoblastic Leukemia (ALL).
Although gene therapy holds great promise for the treatment of diseases it is still a new approach. It possesses several risks such as certain types of cancers, allergic reactions, etc. Genetic therapies are now comparatively safer thanks to recent developments. The FDA has approved various gene transfer therapies for clinical use in the United States due to improved safety. Researchers are still studying other risks and they hope that in the near future, they will be able to develop new methods that will help in eliminating those risks so that this gene therapy will be used worldwide to treat diseases.
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