CRISPR Genomics Precision Medicine

The State of Gene Therapies

Nima Karimi — McMaster University Health Sciences 2023

As the quest of mankind for optimal health continues,  different avenues for achieving this goal have emerged. One area, in particular, is looking at the role of genes in the pathophysiology of diseases, and consequently, investigating therapeutics that target those genes. Genes are the basic functional unit of heredity (1); in other words, they determine your height, the color of your eye and hair, and many other biological traits. Importantly, alterations of the genes and genome have been consistently linked to many pathological conditions. Cystic fibrosis (CF), sickle-cell anemia, and Huntington’s disease are some of the more prominent examples of genetic disorders (2). As these conditions have led to increased mortality and reduced quality of life, the scientific community has searched for potential therapeutics; one, in particular, being gene therapy.

The first human studies on gene therapy were done in the early 1990s. One such experiment involved the transfer of genes coding for a specific enzyme, to patients with severe combined immunodeficiency, which showed promising results (3). Since then, research into gene therapy has grown considerably. More recently, some studies have used gene therapy to treat CF, a progressive genetic condition that leads to the loss of lung function with no current treatment (4). Interestingly, the use of gene therapy in CF patients have shown to improve lung capacity (3). With CF being one of the most prevalent genetic disorders, the use of gene therapy shows a promising future for the treatment of this condition.

Now you may be wondering to yourself, how is genetic therapy actually done? Generally speaking, gene therapy involves the identification of cell types and DNA sequences that are defective, and then introducing a new DNA sequence containing the functional genes to offset the effects of the disease-causing genetic alterations (5). There are two different approaches to gene therapy (figure 1), and these involve alterations of different types of cells (6). Somatic gene therapy involves the transfer of DNA to different cells in our body that do not produce sperm or eggs. Given that these changes are not in the germline, any DNA alteration cannot be passed on from parents to their children (6). In contrast, germline gene therapy involves the transfer of DNA to cells that produce eggs or sperms, meaning these changes can be inherited (6).

Additionally, various techniques are being used in gene therapy. One such technique is gene augmentation therapy (6). This technique can be used to treat genetic abnormalities  that stem from mutation, where the gene in question does not produce its functional products (6, 7). As shown in figure 2, this therapy adds the DNA containing a functional gene back into the cell that is defective and ultimately, can reverse the abnormality (8). Another technique involves gene inhibition (6). This technique can be used in pathologies in which the overexpression of certain genes is causing the disease. In this approach, the aim is to introduce a new gene that either inhibits the expression of another faulty gene, or interferes with the activity of the product produced by the faulty gene (9), as shown in figure 3.

Overall, it is clear that gene therapy presents a very promising future for the treatment and management of diseases that were once deemed incurable. Today, there are more than 600 genes and cellular therapies that are being researched (10). In the coming years, one could expect the emergence of many genetic therapies for common and rare conditions. This emergence could both provide treatments for patients that lack therapeutics today, and also improve their overall quality of life.


1.         Kitcher P. Genes. The British Journal for the Philosophy of Science. 1982;33(4):337-59.

2.         Conrad Stöppler M. Genetic Diseases (Disorder Definition, Types, and Examples): MedicineNet;  [Available from:

3.         Steffin DHM, Hsieh EM, Rouce RH. Gene Therapy: Current Applications and Future Possibilities. Advances in Pediatrics. 2019;66:37-54.

4.         Davis PB. Cystic Fibrosis Since 1938. American Journal of Respiratory and Critical Care Medicine. 2006;173(5):475-82.

5.         Verma IM, Naldini L, Kafri T, Miyoshi H, Takahashi M, Blömer U, et al., editors. Gene Therapy: Promises, Problems and Prospects. Genes and Resistance to Disease; 2000 2000//; Berlin, Heidelberg: Springer Berlin Heidelberg.

6.         What is gene therapy? 2021 [Available from:

7.         Frazier S. Embryo Gene Editing: Changing Life As We Know It 2019 [Available from:

8.         Nóbrega C, Mendonça L, Matos CA. Gene Therapy Strategies: Gene Augmentation. In: Nóbrega C, Mendonça L, Matos CA, editors. A Handbook of Gene and Cell Therapy. Cham: Springer International Publishing; 2020. p. 117-26.

9.         James W. Towards Gene-Inhibition Therapy: A Review of Progress and Prospects in the Field of Antiviral Antisense Nucleic Acids and Ribozymes. Antiviral Chemistry and Chemotherapy. 1991;2(4):191-214.

10.       Dorholt M. We’re on the Verge of a Breakthrough for Gene Therapies 2021 [Available from:

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