RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding.
After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells.
Our results establish CRISPR–Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development.
Chronic wounds do not heal in an orderly fashion in part due to the lack of timely release of biological factors essential for healing. Topical administration of various therapeutic factors at different stages is shown to enhance the healing rate of chronic wounds. Developing a wound dressing that can deliver biomolecules with a predetermined spatial and temporal pattern would be beneficial for effective treatment of chronic wounds. Here, an actively controlled wound dressing is fabricated using composite fibers with a core electrical heater covered by a layer of hydrogel containing thermoresponsive drug carriers. The fibers are loaded with different drugs and biological factors and are then assembled using textile processes to create a flexible and wearable wound dressing. These fibers can be individually addressed to enable on-demand release of different drugs with a controlled temporal profile. Here, the effectiveness of the engineered dressing for on-demand release of antibiotics and vascular endothelial growth factor (VEGF) is demonstrated for eliminating bacterial infection and inducing angiogenesis in vitro. The effectiveness of the VEGF release on improving healing rate is also demonstrated in a murine model of diabetic wounds.
Instead of plain sterile cotton or other fibers, this dressing is made of “composite fibers with a core electrical heater covered by a layer of hydrogel containing thermoresponsive drug carriers,” which really says it all.
It acts as a regular bandage, protecting the injury from exposure and so on, but attached to it is a stamp-sized microcontroller. When prompted by an app (or an onboard timer, or conceivably sensors woven into the bandage), the microcontroller sends a voltage through certain of the fibers, warming them and activating the medications lying dormant in the hydrogel.
Those medications could be anything from topical anesthetics to antibiotics to more sophisticated things like growth hormones that accelerate healing. More voltage, more medication — and each fiber can carry a different one.
On it are the PowerPoint slides of his next big project, a breathtaking $100 million, five-year proposal focused on paralysis, depression, amputation, epilepsy, and Parkinson’s disease. Herr is still trying to raise the money, and the work will be funneled through his new brainchild, MIT’s Center for Extreme Bionics, a team of faculty and researchers assembled in 2014 that he codirects. After exploring various interventions for each condition, Herr and his colleagues will apply to the FDA to conduct human trials. One to-be-explored intervention in the brain might, with the right molecular knobs turned, augment empathy. “If we increase human empathy by 30 percent, would we still have war?” Herr asks. “We may not.”
The idea of an endlessly upgradable human is something Herr feels in his bones. “I believe in the near future, in a decade or two, when you walk down the streets of Boston, you’ll routinely see people wearing bionic systems,” Herr told ABC News in a 2016 interview. In 100 years, he thinks the human form will be unrecognizable. The inference is that the abnormal will be normal, beauty rethought and reborn. Unusual people like Herr will have come home.
Hugh Herr is building the next generation of bionic limbs, robotic prosthetics inspired by nature’s own designs. Herr lost both legs in a climbing accident 30 years ago; now, as the head of the MIT Media Lab’s Biomechatronics group, he shows his incredible technology in a talk that’s both technical and deeply personal — with the help of ballroom dancer Adrianne Haslet-Davis, who lost her left leg in the 2013 Boston Marathon bombing, and performs again for the first time on the TED stage.
Addressing disabilities is just the beginning. You can tell that Herr wants bionic prosthetics to augment humans beyond their limits.
An incredible TED Talk.
a group of researchers at MIT have developed a remote sleep sensing system that uses radio waves to capture data about your brain waves while you sleep–and AI to read them–without ever touching your body. It consists of a laptop-sized wireless device that emits radio signals. When put in the user’s bedroom, the waves detect even the slightest movement of the body. The system doesn’t just do the job of a sleep-tracking wearable without the wearable; it also just provides data at a similar level of accuracy as a sleep lab.
In order to cut out all the extraneous information her system records, she developed a machine learning algorithm that can extract sleep stages–light, deep, and REM sleep–out of the mess of data. The algorithm was trained on a sleep dataset of 25 individuals for a total of 100 nights of sleep, taken using an FDA-approved device that uses EEG to record brain waves.
The results are 80% accurate