[Researcher of the Month] When Exception Becomes a New Finding
Professor Bae Sangsu (Department of Chemistry)
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The Human Genome Project (HGP) was an international, collaborative research program that clinched complete mapping and understanding of human genes. HGP offered clues to the resolution of diseases through genetic modifications. The base editors – which inserts, deletes, modifies, and replaces targeted DNA in a genome with engineered nucleases – are technological embodiments that integrate follow-up studies from HGP. Professor Bae Sangsu (Department of Chemistry), who has pointed out unreported issues in Adenine base editors, shared his insights with us.
Base editing technology has undergone technological innovations in the last decade. The CRISPR gene editing is the third-generation base editor following zinc finger nuclease (ZFN) gene editing and transcription activator-like effector nucleases (TALENs) gene editing. The method allows the cell’s genome to be cut at the desired location by using a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. The CRISPR gene editing was selected as the 2015 Breakthrough of the Year by Science.
The base editing systems are now more influenced by nucleic acid sequences. A nucleic acid sequence is a succession of base-pairs signified by a series of Adenine, Guanine, Cytosine, and Thymine, which determines the biological characteristics of a living organism. Cytosine base editors (CBEs) and adenine base editors (ABEs) are the two major base editors that efficiently enable base substitutions.
Recently, some researchers have reported their observations of unexpected ABE-induced cytosine conversions in mouse embryos. These conversions were thought to be exceptional cases. However, Bae’s research team found out that ABEs convert cytosine to guanine or thymine in a narrow editing window and a confined TC*N sequence context.
“What we found is that cytosine conversion in ABE is a systematic consequence in a certain situation,” said Bae. “Our findings are like bugs in smartphone applications.” This research has proven that the ABE cytosine deamination activity is relatively minor compared to the canonical ABE adenine deamination activity, but is an independent one.
“It is clear that CRISPR-based base editing technologies have advanced the genome-editing field,” said Bae. The professor is looking forward to making a better tool by overcoming these unexpected results. His research team is working to develop ABE which does not convert Cytosine as an improvement study. At the same time, Bae is also involved in developing a more efficient CBE through his findings.
Some say that even a minor error may turn out to be the one thing necessary to a worthwhile achievement. Bae’s effort to systemize exceptions are set to support the quality of human life by enhancement in base editing technology.
Oh Kyu-jin firstname.lastname@example.org
Photos by Kim Ju-eun
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