Exploring Gene Therapy: A Transformative Field in Modern Medicine

Gene therapy has quickly become one of the most exciting topics in the world of science. This method gained widespread attention after major milestones such as the 2020 Nobel Prize for CRISPR technology, the first application of gene editing in infants to treat HIV by Chinese doctor, and novel treatments for diseases like SMA. But what is gene therapy all about?

DNA: Gene Therapy

DNA, the fundamental building block of life, can undergo mutations over time due to various reasons, which can lead to changes in its nucleotide sequence. Most of the time, these changes are harmless, but sometimes they can affect how our cells work and result in diseases. Mutations can be inherited from parents or occur later due to environmental factors, such as sun exposure. Unfortunately, many people suffer from severe genetic diseases, including cancer, and standard treatments may be insufficient. For this reason, researchers are making significant efforts to develop new approaches.

A Brief History of Gene Therapy

The history of gene therapy dates back to the 1960s, but the first clinical trial took place in 1990 with a child suffering from severe combined immunodeficiency (SCID). Initially, promising results were observed. However, in the following years, some patients developed treatment-related leukemia, and one died from a severe immune response triggered by the treatment. As a result, scientists returned to the lab to investigate the causes of these complications. Eventually, these issues were largely resolved, clinical trials resumed, and the field entered a period of rapid development.

In 2003, Gendicine, a gene therapy designed for cancer, was developed in China and became the world’s first approved gene therapy treatment. The first gene therapy medicine authorized in Europe was Glybera, a treatment for a rare genetic disease, approved in 2012. In 2017, Kymriah (tisagenlecleucel) became the first gene therapy approved by the FDA in the U.S. for treating acute lymphoblastic leukemia (ALL). With the introduction of CRISPR technologies, the field has become even more intriguing. To date, the FDA has approved 43 gene therapy drugs, and there are more than 5,000 clinical trials currently underway.

So, What exactly Is Gene Therapy?

Gene therapy involves replacing a defective gene that causes a disorder with a functional one, aiming to address the root cause of the illness. The goal is to cure the disease by transferring a healthy gene into the affected cell using vectors that can transport nucleic acids (DNA or RNA). This process works by either replacing the defective gene, silencing a mutated gene, or inserting a healthy gene.

There are two types of gene therapy: ex-vivo and in-vivo. In ex-vivo therapy, the patient’s diseased cells are removed, modified in a lab, and then reintroduced into the patient’s body. In in-vivo therapy, the treatment is delivered directly into the body.

Gene Therapy

One of the most critical factors in designing gene therapies is choosing the right delivery method (vector) to transport nucleic acids into the patient’s cells. This directly affects the efficiency of the treatment, making vector selection vital. While various vectors are available, viruses are the most commonly used due to their natural ability to effectively transport genetic material.

In the lab, scientists disable the virus’s ability to cause disease and insert the therapeutic DNA into the virus, ensuring it won’t harm the patient once administered. Other vectors, such as liposomes, peptides, and nanoparticles, are also used, and research is continuously expanding to improve treatment efficacy.

Can Genetic Modifications Be Inherited?

One frequently asked question is whether genetic modifications from gene therapy can be inherited by future generations. Our bodies have two types of cells: somatic cells, which make up most of the body, and germ cells, which produce reproductive cells. Changes made in somatic cells cannot be passed on to future generations, but modifications in germ cells (known as germline therapy) can be inherited. Due to the ethical concerns surrounding germline therapies, they are not currently supported by regulatory authorities.

What Diseases Can Be Treated with Gene Therapy?

Gene therapy is currently being developed to treat a wide range of disorders. It offers potential solutions for diseases such as cancer, immune deficiencies, rare genetic disorders, infectious diseases, and neurological, eye, cardiovascular, and blood conditions. Each disease and its associated genes are unique, requiring tailored approaches and studies.

Advantage & Disadvantage

One of the key advantages of gene therapy is its ability to address the root cause of the disease. Some treatments only require a single dose, offering the possibility of a cure with one administration. However, the major disadvantage is the high cost of these treatments, which is beyond the reach of many patients. Additionally, since viruses are often used as vectors, there is a risk of immune reactions, although this risk has been significantly reduced with current advancements.

While gene therapy has had a mixed history, it is a promising method that has the potential to revolutionize how we treat diseases and offer solutions to patients who previously had no hope. It has already saved many lives, and with ongoing clinical trials worldwide, it holds the potential to save many more in the future.

References

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3)Capone, F., Nappi, F., & Galli, M. C. (2020). Gene Therapy Clinical Trials: Past, Present and Future. In Second Generation Cell and Gene-based Therapies (pp. 285-301). Academic Press.

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