Genome editing is a topic which has been on the forefront of medical discussion for years. After all, gene editing allows for the potential to treat – or even cure – a variety of genetic conditions. According to Medical XPress, researchers from the Ohio State University Wexner Medical Center and College of Medicine recently modified a base editing technique to create a novel approach to addressing Duchenne muscular dystrophy (DMD) genetic mutations in mice models. See the full study findings published in Nature Communications.

Base Editing

Typically, a great deal of discussion on gene editing centers around CRISPR-Cas9 (“CRISPR”). When using CRISPR, scientists can alter and correct genetic mutations which cause genetic disorders or conditions. However, there is also some controversy around CRISPR. For example, cutting DNA can ultimately damage health. Additionally, the relationship between CRISPR and the development of off-target mutations is still being determined. Thus, researchers wanted to understand if another form of gene editing could be more beneficial.

Within this study, researchers built off of CRISPR technology and used base editing. In Genetic Engineering & Biotechnology News, the author quotes Dr. Alexis Komor, PhD, as describing base editing as:

a therapeutic to correct disease-relevant point mutations [that can also] introduce these point mutations into the genome of live cells.

In short, base editing offers the opportunity to edit DNA bases – A, G, T, and C – to fix or treat some form of disease-causing mutation. To evaluate this new gene editing tool for DMD, researchers modified a base editor. Next, they evaluated the treatment within adult mice models of DMD. Using this tool, researchers were able to not only edit the mutation without cutting or damaging any DNA but were able to deliver the editor via an adeno-associated virus (AAV). Ultimately, researchers determined that:

• This new base editing technique restored dystrophin expression in mice hearts and muscles.
• Only one singular intravenously administered treatment was needed for sustained responses. For example, mice models who received the adenine base editor at 5 weeks old saw, by 10 months old, a significant improvement in dystrophin expression (95%).
• Additionally, the treatment was relatively safe and well-tolerated. No adverse reactions occurred.

While additional preclinical testing is needed, this study shows that modified base editing technology could show promise for treating DMD and other genetic disorders in the future.

Duchenne Muscular Dystrophy (DMD)

DMD gene mutations cause Duchenne muscular dystrophy (DMD). Normally, DMD encodes for the production of dystrophin, which helps to strengthen muscle fiber and prevent muscular injuries. However, these genetic mutations prevent patients from creating dystrophin. As a result, muscle weakness and wasting occur. Because DMD is inherited in an X-linked recessive pattern, it is extremely rare for females to have. Only 1 in around 50 million female births has DMD, compared to 1 in 3,500 male births. Typically, symptoms appear before age 6. Symptoms include:

• Frequent tripping and falling
• Difficulty jumping, running, or walking
• Fatigue
• Progressive muscle weakness which begins in the legs, pelvis, and thighs
• Delayed motor skill development
• Joint contractures
• Enlarged calves
• Scoliosis
• A waddling gait
• Heart disease
• Respiratory failure