(Reuters) — AstraZeneca has been granted protection from future product liability claims related to its COVID-19 vaccine hopeful by most of the countries with which it has struck supply agreements, a senior executive told Reuters.
CRISPR-Cas9 base editors comprise RNA-guided Cas proteins fused to an enzyme that can deaminate a DNA nucleoside. No natural enzyme deaminates adenine in DNA, and so a breakthrough came when a natural transfer RNA deaminase was fused to Cas9 and evolved to give an adenine base editor (ABE) that works on DNA. Further evolution provided the enzyme ABE8e, which catalyzes deamination more than 1000 times faster than early ABEs. Lapinaite et al. now present a 3.2-angstrom resolution structure of ABE8e bound to DNA in which the target adenine is replaced with an analog designed to trap the catalytic conformation. The structure, together with kinetic data comparing ABE8e to earlier ABEs, explains how ABE8e edits DNA bases and could inform future base-editor design.
Science, this issue p. 566
CRISPR-Cas–guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo–electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that ABE8e catalyzes DNA deamination up to ~1100-fold faster than earlier ABEs because of mutations that stabilize DNA substrates in a constrained, transfer RNA–like conformation. Furthermore, ABE8e’s accelerated DNA deamination suggests a previously unobserved transient DNA melting that may occur during double-stranded DNA surveillance by CRISPR-Cas9. These results explain ABE8e-mediated base-editing outcomes and inform the future design of base editors.
Steve Granick, Director of the IBS Center for Soft and Living Matter and Dr. Huan Wang, Senior Research Fellow, report together with 5 interdisciplinary colleagues in the July 31 issue of the journal Science that common chemical reactions accelerate Brownian diffusion by sending long-range ripples into the surrounding solvent.
The findings violate a central dogma of chemistry, that molecular diffusion and chemical reaction are unrelated. To observe that molecules are energized by chemical reaction is “new and unknown,” said Granick. “When one substance transforms to another by breaking and forming bonds, this actually makes the molecules move more rapidly. It’s as if the chemical reactions stir themselves naturally.”
“Currently, nature does an excellent job of producing molecular machines but in the natural world scientists have not understood well enough how to design this property,” said Wang. “Beyond curiosity to understand the world, we hope that practically this can become useful in guiding thinking about transducing chemical energy for molecular motion in liquids, for nanorobotics, precision medicine and greener material synthesis.”
Mathematicians typically appreciate either generic or exceptional beauty in their work, but one type is more useful in describing the universe.
At the heart of every white dwarf star—the dense stellar object that remains after a star has burned away its fuel reserve of gases as it nears the end of its life cycle—lies a quantum conundrum: as white dwarfs add mass, they shrink in size, until they become so small and tightly compacted that they cannot sustain themselves, collapsing into a neutron star.
This puzzling relationship between a white dwarf’s mass and size, called the mass-radius relation, was first theorized by Nobel Prize-winning astrophysicist Subrahmanyan Chandrasekhar in the 1930s. Now, a team of Johns Hopkins astrophysicists has developed a method to observe the phenomenon itself using astronomical data collected by the Sloan Digital Sky Survey and a recent dataset released by the Gaia Space Observatory. The combined datasets provided more than 3,000 white dwarfs for the team to study.
A report of their findings, led by Hopkins senior Vedant Chandra, is now in press in Astrophysical Journal and available online on arXiv.
The next Mars rover mission, Perseverance, is on its way to the Red Planet to look for signs of ancient life and collect samples for return to Earth.
No offense to Volkswagen’s ID. Buzz, a successful design in its own right, but when we close our eyes and imagine an all-electric Volkswagen Type 2 for the 21st century, it’s the new eBussy that we see. That was true before we knew it existed, and it’s definitely true now that we’ve seen the actual design. Beyond timelessly simple styling, the new German-designed electric mini-bus also promises some of the most impressive modularity out there, switching between family van, cargo van, pickup truck, camper van, off-road adventure van and other configurations. And so far, it looks to be surprisingly affordable.
Volkswagen has given its own electric van concepts more of a futuristic identity, but Münster-based ElectricBrands keeps things more traditional. Its eBussy design looks very much like a T1/T2 Transporter, reinterpreted for modern times. It has the flat face, bright, round headlamps, softened-box body and partially covered rear wheels. Every time we stare it in the eyes, we see “T2 of the digital age” staring back at us.
Like those early VW Type 2’s, the eBussy isn’t a vehicle so much as the platform for an entire family of vehicles, ranging from flatbed and tipper trucks to delivery, family and camper vans. That modularity isn’t just a handy available feature, it’s THE feature that the eBussy design was based around, the idea being that owners can easily swap out individual modules to make one vehicle into any and every vehicle for all their passenger and cargo-hauling needs. ElectricBrands promises Lego-like simplicity in plugging and playing.
Within a mere eight years, CRISPR-Cas9 has become the go-to genome editor for both basic research and gene therapy. But CRISPR-Cas9 also has spawned other potentially powerful DNA manipulation tools that could help fix genetic mutations responsible for hereditary diseases.
Researchers at the University of California, Berkeley, have now obtained the first 3D structure of one of the most promising of these tools: base editors, which bind to DNA and, instead of cutting, precisely replace one nucleotide with another.
First created four years ago, base editors are already being used in attempts to correct single-nucleotide mutations in the human genome. Base editors now available could address about 60% of all known genetic diseases—potentially more than 15,000 inherited disorders—caused by a mutation in only one nucleotide.
A new AI algorithm developed by the University of Pittsburgh has achieved the highest accuracy to date in identifying prostate cancer, with 98% sensitivity and 97% specificity.
It’s the banking world’s version of the rich getting richer.
A record $2 trillion surge in cash hit the deposit accounts of U.S. banks since the coronavirus first struck the U.S. in January, according to FDIC data.
The wall of money flowing into banks has no precedent in history: in April alone, deposits grew by $865 billion, more than the previous record for an entire year.
