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Home›Economic integration›Scientists develop new gene editor to correct pathogenic mutations

Scientists develop new gene editor to correct pathogenic mutations

By Susan Weiner
May 23, 2021
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CRISPR-based gene editor, C-to-G Base Editor (CGBE), opens up treatment avenues for up to 40% of genetic disorders caused by single-nucleotide mutations.

A team of researchers from the Genome Institute of Singapore (GIS) of the Agency for Science, Technology and Research (A * STAR) has developed a CRISPR-based gene editor, C-to-G Base Editor (CGBE) , to correct mutations that cause genetic disorders. Their research was published in Nature communications March 2, 2021.

One in seventeen people in the world suffers from some type of genetic disorder. Chances are you or someone you know – a relative, friend or colleague – is one of the approximately 450 million people affected worldwide. The mutations responsible for these disorders can be caused by several mutagens – from sunlight to spontaneous errors in your cells. By far the most common mutation is single base substitution, in which a single base in the DNA (like G) is replaced by another base (like C). Countless cystic fibrosis patients around the world have C instead of G, resulting in defective proteins that cause genetic disease. In another case, the replacement of A by T in hemoglobin causes sickle cell anemia.

To correct these substitutions, the team invented a CRISPR-based gene editor that precisely alters defective C in the genome into G. single-base substitutions that are associated with human diseases such as the aforementioned cystic fibrosis, cardiovascular disease, musculoskeletal disease and neurological disorders.

CGBE CRISPR based gene editor

The CRISPR-based gene editor, CGBE, opens up treatment avenues for genetic disorders caused by single-nucleotide mutations. C-to-G Basic Editor (CGBE) converts C in genes to G. This invention corrects pathogenic mutations into healthy versions, enabling treatment of genetic diseases. Credit: Agency for Science, Technology and Research (A * STAR), Singapore Genome Institute (GIS)

CGBE editor advances widely adopted CRISPR-Cas9 technology to enable molecular surgery on the human genome. CRISPR-Cas9 technology is commonly used to disrupt target genes, but it is inefficient when a precise change in particular sequences is desired. The CGBE editor solves a key aspect of this challenge by enabling efficient and precise genetic changes. The CGBE consists of three parts: 1) a modified CRISPR-Cas9 will locate the mutant gene and focus the entire editor on that gene; 2) a deaminase (an enzyme that removes the amino group of a compound) will then target the defective C, and mark it for replacement, and 3) finally, a protein will initiate cellular mechanisms to replace that defective C with a G. This allows for a hitherto impossible direct conversion from C to G, correcting the mutation and, therefore, treating the genetic disorder.

Dr Chew Wei Leong, Principal Investigator at GIS, said: “The CGBE gene editor is a revolutionary invention that, for the first time, directly converts C to G in genes, potentially opening up treatment avenues for a substantial fraction of genetics. disorders associated with single nucleotide mutations. “

“Patient safety is essential,” said Dr Chew. “We are working to ensure that our CGBE and CRISPR-Cas modalities are both effective and safe in disease models before we can further develop these modalities for the clinic. For his scientific efforts in gene editing therapy, he was one of three young researchers who won the prestigious Young Scientist Award (YSA) 2020.

Professor Patrick Tan, Executive Director of SIG, said: “New editors such as CGBE expand the growing range of precise genome editing tools that include Cytidine Base Editors (CBEs), Base Editors adenine (ABE), CGBEs and major publishers. Together, they enable precise and efficient engineering of DNA for research, biological interrogation, and disease correction, ushering in a new era of genetic medicine.

Reference: “Editing the Programmable C: G to G: C Genome with CRISPR-Cas9 Directed Base Excision Repair Proteins” by Liwei Chen, Jung Eun Park, Peter Paa, Priscilla D. Rajakumar, Hong-Ting Prekop, Yi Ting Chew, Swathi N. Manivannan and Wei Leong Chew, March 2, 2021, Nature communications.
DOI: 10.1038 / s41467-021-21559-9

About the A * STAR Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A * STAR). He has a global vision that seeks to use genomic science to achieve extraordinary improvements in human health and public prosperity. Created in 2000 as a genomics discovery center, the SIG pursues the integration of technology, genetics and biology for an academic, economic and societal impact, with the mission of “reading, revealing and writing ‘DNA for a better Singapore and a better world’.

Key research areas of GIS include precision medicine and population genomics, genome informatics, space and single-cell systems, epigenetic and epitranscriptomic regulation, genome architecture and design, and platforms for sequencing. The GIS genomic infrastructure is also used to train new scientific talent, to function as a bridge for academic and industrial research and to explore high-impact scientific questions.

About the Agency for Science, Technology and Research (A * STAR)

The Agency for Science, Technology and Research (A * STAR) is Singapore’s leading public sector agency leading economically oriented research to advance scientific discovery and develop innovative technologies. Through open innovation, we collaborate with our partners in the public and private sectors for the benefit of society.

As a science and technology organization, A * STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and improves lives by contributing to societal benefits such as improved healthcare outcomes, urban living and sustainability.

We play a key role in nurturing and developing a diversity of talents and leaders within our agency and research units, the broader research community and the industry. A * STAR’s R&D activities cover biomedical sciences, physical sciences and engineering, with research entities mainly located in Biopolis and Fusionopolis.



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