Nav: Home

Unconstrained genome targeting with CRISPR-Cas9 variants less reliant on PAM

March 26, 2020

Addressing a fundamental limitation in CRISPR-Cas genome editing, researchers have developed new engineered Cas9 variants that nearly eliminate the need for a protospacer adjacent motif known as PAM. This motif is otherwise required for DNA-targeting CRISPR enzymes. According to the report, the novel Cas9 enzymes open up virtually the entire genome for targeting, with unprecedented accuracy. This drastically expands the potential of CRISPR-Cas systems, the authors say, something they showed by using their approach to correct mutations associated with human diseases located in previously "un-editable" regions of the genome. DNA-targeting CRISPR-associated enzymes find their targets by recognizing protospacer adjacent motif (PAM) sequences - short bits of genetic code that flag editable sections of DNA and serve as a binding signal for specific CRISPR-Cas nucleases. Without an adjacent, recognizable PAM sequence, a Cas enzyme will not recognize nor successfully attach to and cleave a desired section of DNA. While different Cas enzymes, including variants of the canonical Streptococcus pyogenes Cas9 (SpCas9), recognize different PAM sequences, much of the genome remains un-targetable for editing or more prone to generating off-target mutations. Thus, the PAM requirement represents a significant limiting barrier for applications that require high-resolution genome targeting. To address this limitation, Russell Walton and colleagues engineered new variants of the SpCas9 enzyme capable of targeting and editing sequences bearing a wider array of PAMs. Here, Walton et al. report on two significant variants: SpG, which is capable of targeting an expanded set of NGN PAMs, and a near-PAMless variant called SpRY. Collectively, SpG and SpRY enable unconstrained targeting using CRISPR-Cas9 nucleases across nearly the entire genome and with single base pair precision. Using SpRY, the authors were able to correct mutations associated with human diseases located in previously "un-editable" regions of the genome.
-end-


American Association for the Advancement of Science

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.