inherited diseases

To this point, inherited diseases such as sickle cell disease and β-thalassaemia have been managed by medical treatment, but no cure has been found. Developments in genetic engineering have allowed researchers to investigate gene editing as a cure for these innate diseases with promising results.


While many diseases are contracted and can be cured by modern medicine, others are congenital (from birth) and are not so easily treated. The latter are inherited diseases, or genetic disorders, which stem from a genetic defect that adversely affects an individual’s quality of life. Genetic disorders can have varying degrees of impact, some leading to infant mortality, while others can remain largely undetected into adulthood.

Since inherited diseases stem from an individual’s DNA, they are difficult to treat and to this point have been impossible to cure. The cause of the disease stays with the patient and doctors can only manage its symptoms. However, advancements in genetic engineering provide the potential to safely change an individual’s DNA, repairing defects and curing genetic disorders.

In a recent study, Bahal et al. investigated a new method for repairing DNA in mice. Published in Nature Communications, the study used mice with β-thalassaemia, an inherited disease that causes anemia, or a decrease in red blood cells. This can lead to complications if the disease is misdiagnosed, because while typical anemia is due to low iron levels, β-thalassaemia-derived anemia has other causes. Thus, the typical treatment of iron supplementation prescribed to anemia can cause toxic blood iron levels in β-thalassaemia patients. The researchers used PNA/DNA/PNA triplexes, structures that can bind to the DNA backbone, to repair the defected areas. The triplexes were designed to bind specifically to defective sites causing β-thalassaemia, and upon binding they attract DNA repair mechanisms to the attached site.

The results of the study showed that this new method of gene editing was effective enough to cure the disease phenotype (the symptoms of a specific gene). The mice’s anemia was relieved for 140 days post-treatment, and other signs of β-thalassaemia were reduced, such as improvements in red blood cell structure and decreased splenomegaly (enlargement of the spleen). There were also very low off-target effects measured, indicating a high triplex specificity and thus low chance of adverse effects caused by DNA misrepair.

The results of this study show promise in further exploration of this gene-editing technique as a treatment method for β-thalassaemia in humans. Other work also shows potential for use of this method in treating other genetic disorders, such as cystic fibrosis. Modifications to the triplex mechanisms could lead to improvements in the gene editing process, and should be investigated as we move towards clinical utility.


Written By: Wesley Tin, BMSc

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