AsianScientist (Jun. 10, 2021) – With the help of Nobel Prize-winning technology CRISPR/Cas9, scientists from Singapore have developed a gene editor that can precisely correct single letter mutations that cause genetic disorders. Their research was published in Nature Communications.
Worldwide, one in every 17 people live with a genetic disorder. Whether it’s a relative, friend or colleague, chances are you personally know one of the approximately 450 million people affected globally with such disorders. Given that trillions of cells within our body divide each day, mutations can easily arise, driven by mutagens ranging from sunlight to spontaneous errors.
Among the many types of genetic mutations, the most common by far is known as the single-base substitution, where a single DNA base is replaced by another. In cystic fibrosis, for instance, the base cytosine (C) is replaced by guanine (G) in the CFTR gene, which regulates the balance of salt and water in our bodies. Accordingly, cystic fibrosis patients often have difficulty breathing as the malfunctioning CFTR gene results in thick secretions in the lungs.
To fix detrimental single-base substitutions, a team led by Dr. Chew Wei Leong from Singapore’s Agency for Science, Technology and Research (A*STAR) developed a first-of-its-kind gene editor that precisely changes defective Cs in the genome to Gs.
The team achieved this milestone by improving upon existing CRISPR/Cas9 gene editing technology. While CRISPR/Cas9 is commonly used to edit stretches of genes, it remains inefficient when a precise, single-letter change to a specific sequence is needed. The team’s C-to-G base editor addresses this in three parts: first, a CRISPR/Cas9 system is modified to home in on the mutant gene.
An enzyme then marks the defective C for replacement by removing its amino group, after which repair proteins excise C and replace it with a G. The team applied their new base editor to correct mutations in genes like GJB2, which is linked to hearing loss, and ADRB2, which is associated with imbalanced lipid levels.
“The C-to-G base editor is a ground-breaking invention that…potentially opens up treatment avenues for a substantial fraction of genetic disorders associated with single-nucleotide mutations,” concluded Chew. “We are working to ensure our [base editor] and CRISPR/Cas9 modalities are both effective and safe in disease models before we can further develop [them] for the clinic.”
The article can be found at: Chen et al. (2021) Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins.
Source: A*STAR; Photo: Shutterstock.
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