The NgAgo saga’s twisty road

Written by Nathan Blow

New twists in the case of proposed genome editing technology based on NgAgo are putting this protein back in the spotlight. But as answers start to emerge, even more questions creep up.

By December 2016, most researchers thought the NgAgo genome editing technology reported in Nature Biotechnology by Han Chunyu and colleagues at Hebei University of Science and Technology was down for the count. Since the initial publication, there have been no reports confirming that authors’ asseration that NgAgo could be used for genome editing in a manner similar to CRISPR/Cas9. However, reports have appeared in blogs and peer-reviewed articles showing that NgAgo is doing something in cells—possibly silencing genes.

Now, a new manuscript posted on the bioRxiv pre-print server on January 20, 2017 suggests a possible reason for the disparate results. NgAgo does not cleave DNA as initially suggested; instead the protein cleaves RNA.

In this manuscript, Jin-Soo Kim and colleagues at the Seoul National University in South Korea describe a series of experiments showing that NgAgo can use oligodeoxyribonucleotides of variable lengths to cleave RNA targets into multiple smaller fragments. Kim and his co-authors hypothesize that NgAgo acts in host cells as a defense against mobile genetic elements by degrading RNA strands in RNA-DNA duplexes. While NgAgo may not be a genome editing technology like CRISPR/Cas9, it could be potentially harnessed for use in biomedical applications to examine gene function similar to siRNA technology. Developers seem have taken note of this possibility as well.

Around the time Kim’s manuscript was posted on bioRxiv, Novozyme, a Denmark-based biotechnology company, announced the signing of a cooperation agreement with Hebei University of Science and Technology whereNovozyme stated an interest in exploring possible applications for NgAgo technology. The company has developed numerous microbial enzymes, and has interest in gene silencing technologies. Specific details on the agreement are not yet available.

Just when it seems that the biological mechanism is coming to light, Kim reportedly filed a patent on the use of NgAgo in gene-silencing applications, which could lead to questions over intellectual property and further cloud the future of NgAgo technology.