Science Concentrates BIOTECHNOLOGY
CRISPR can now edit RNA team modified Cas13b so that it binds RNA tial applications for REPAIR. For example, As CRISPR gene editing marches closer to RNA editing could serve as a short-term but doesn’t cut it, and then they attached the clinic, several researchers have been therapy during wound healing and inflamtinkering to unleash the DNA editor on an- part of a second enzyme, called ADAR, mation by modulating the activity or levels that converts an A nucleotide to the nonother nucleic acid: RNA, the intermediary of RNA that produce proteins involved in standard nucleotide inosine (I). The cell’s messenger between DNA and proteins. those processes. protein synthesis machinery then reads A team led by Feng Zhang of Broad “Applications of the CRISPR system the I as a G. Zhang calls the whole system Institute of MIT & Harvard now reports to RNA are heating up,” says Gene Yeo, a RNA Editing for Programmable A to I Rethe first CRISPR complex engineered to researcher at the University of California, placement (REPAIR). edit individual bases of RNA (Science 2017, San Diego, who developed a version of The team showed that REPAIR could DOI: 10.1126/science.aaq0180). Cas9 to target and cleave RNA. correct 35% and 23% of the mutations “This is quite exciting, and I am talking about a competitor here, mRNA (to be edited) so I shouldn’t be excited,” ADAR Cas13b Guide RNA says Mitchell R. O’Connell, A I who studies CRISPR RNA targeting at the University of 5´ 3´ Rochester Medical Center. ADAR deaminates Guide RNA directs RNA editors will be valuable adenosine to inosine Cas13b to instruments for controlling complementary mRNA gene expression in the lab, O’Connell says. And as a potential therapy, RNA editing A sequence on the guide RNA (red) directs Cas13b to a complementary sequence of the target “could be a safer alternative mRNA (gray), where an enzyme called ADAR converts an adenosine (A) into an inosine (I). to gene editing” because Yeo is a cofounder of Locana, a San in the relevant RNAs for two diseases, changes to DNA are permanent, but edits Diego-based start-up developing therapies X-linked nephrogenic diabetes insipidus to RNA are temporary since cells make for conditions, such as amyotrophic lateral and Fanconi anemia. O’Connell notes the new RNA all the time, he adds. sclerosis, Huntington’s disease, and myosuccess rate is likely to be even lower if The new study comes less than a month tonic dystrophy, involving long, repetitive used in an animal or human, but for some after another publication from Zhang’s stretches of RNA that result in the toxic conditions, it may not be essential to fix lab showing that a CRISPR system with an buildup of proteins. Locana is using Cas 100% of the mutant RNA. enzyme called Cas13a can target and cleave proteins to target and snip these repetitive David B. T. Cox, a graduate student in specific strands of RNA (Nature 2017, DOI: RNA stretches to try to treat the diseases. Zhang’s lab, describes RNA editing as “a 10.1038/nature24049). The classic CRISPR Earlier this year, Yeo demonstrated the direct chemical conversion.” That’s an system uses an enzyme called Cas9 to cut concept in isolated human cells from a advantage over traditional DNA editing, DNA. Both systems require a programmaperson with myotonic dystrophy (Cell ble RNA strand, called a guide RNA, that di- Cox says, which requires cutting the DNA 2017, DOI: 10.1016/j.cell.2017.07.010). strand and could lead to undesired mutarects the Cas enzyme to a complementary “RNA targeting has many advantages, tions. Another new CRISPR tool unveiled target—RNA for Cas13 and DNA for Cas9. and I think this will grow much more this week, called a DNA base editor, can The new RNA editor effectively edits because there are many more things change an A to a G also without snipping an adenosine (A) RNA base to guanosine you can do to RNA than DNA,” Yeo the DNA strand (see page 3). (G). The method is based on yet another Zhang’s team already has a list of poten- says.—RYAN CROSS RNA-targeting enzyme, called Cas13b. The
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C&EN | CEN.ACS.ORG | OCTOBER 30, 2017
The number of recommendations made in the report “Advancing Graduate Education in the Chemical Sciences,” drafted by a commission in 2012. The American Chemical Society organized the study to undertake a wholesale review of graduate education in chemistry. Now, as part of outreach efforts related to its own curriculum reform, a group at the University of Oklahoma wants members from all sectors of the chemistry community to help prioritize implementation of the recommendations. To weigh in on the recommendations by the deadline of Dec. 31, go to http://chemistry.graduate.education. Results of the survey will be available on the website starting Jan. 15, 2018.
C R E D I T: A DA PT E D FRO M S CI E NC E ( G E NE E D I T I N G) ; ACS ( R E P O RT)
New REPAIR system offers a more temporary alternative to DNA editing
