Study shows clinical laboratories may one day use nanorobotic tests to help prevent spread of viral infections, cancer, and other diseases
Scientists from the University of Illinois Urbana-Champaign (U of I) have developed a tiny robotic “hand” made from structural DNA that “grabs” viruses—including the COVID-19 coronavirus—potentially preventing them from infecting cells. Such a nano-robotic antiviral technology could be used by anatomic pathologists and clinical laboratory managers in the future as a point-of-care type of test.
This is yet another example of out-of-the-box thinking by developers of diagnostic technology. Led by Xing Wang, PhD, professor of bioengineering and of chemistry at the U of I, the scientists dubbed their DNA device the NanoGripper.
Similar to a piece of origami (Japanese art of folded paper), the so-called hand has “four bendable fingers and a palm, all in one nanostructure folded from a single piece of DNA,” according to a U of I news release. The scientists found in their study that the hand was capable of doing a rapid test to identify the (COVID-19) virus and “prevented the viral spike proteins from infecting the cells,” Gizmodo reported.
“We are using DNA for its structural properties. It is strong, flexible, and programmable. Yet even in the DNA origami field, this is novel in terms of the design principle. We fold one long strand of DNA back and forth to make all of the elements, both the static and moving pieces, in one step,” said Wang in the news release.
“It would be very difficult to apply it after a person is infected, but there’s a way we could use it as a preventive therapeutic,” said Xing Wang, PhD (above), associate professor, bioengineering and chemistry, University of Illinois Urbana-Champaign, in a news release. “We could make an anti-viral nasal spray compound. The nose is the hot spot for respiratory viruses, like COVID or influenza. A nasal spray with the NanoGripper could prevent inhaled viruses from interacting with the cells in the nose.” Clinical laboratories may one day perform antiviral testing that uses U of I’s NanoGripper technology. (Photo copyright: University of Illinois.)
How a DNA Nanorobot Grabs a Virus
The U of I researchers wanted to leverage what has been discovered about DNA as a “material for constructing versatile nanorobots for biomedical applications,” they wrote in Science Robotics. However, previous studies had not achieved the current origami design of a nanoscale mechanism, the authors added.
With robotic precision and its DNA structure, the researchers’ NanoGripper moves and enables fingers to bend for “customized interactions with target molecules,” Interesting Engineering reported, adding that the technology also:
Employed DNA aptamers on the fingers which act as “molecular locks” to find and bind to specific targets.
In a demonstration, wrapped its fingers around the target spike protein of the COVID-19 coronavirus, essentially “disabling its ability to infect cells.”
“The aptamers are arranged into a spatial pattern that specifically matches that of the trimeric spike protein on the virus outer surface. Such pattern recognition-enabled multivalent interaction—a principle developed by my group—has induced ultrahigh NanoGripper virus-binding avidity, resulting in enhanced virus diagnosis sensitivity,” Wang said.
Taken from the U of I news release, the image above shows how “Inspired by the gripping power of the human hand and bird claws, the researchers designed the NanoGripper with four bendable fingers and a palm, all in one nanostructure folded from a single piece of DNA. Each finger has three joints, like a human finger, and the angle and degree of bending are determined by the design on the DNA scaffold.” Such nano-robotic technology could become a new clinical laboratory test for diagnosing viral infections, or even a preventative treatment if caught prior to infection. (Photo and caption copyright: University of Illinois.)
Developing a Test for COVID-19
The scientists discovered that when equipped with a photonic crystal sensor, NanoGripper detected the SARS-CoV-2 coronavirus in 30 minutes with sensitivity equal to RTqPCR tests, Gizmodo reported.
“The NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of 100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quantitative polymerase chain reaction [RTqPCR],” the authors wrote in Science Robotics.
In fact, the NanoGripper test is reportedly faster and easier than RTqPCR testing, which requires sophisticated instruments.
“Our test is very fast and simple since we detect the intact virus directly,” said study collaborator Brian Cunningham, PhD, professor, electrical and computer engineering and bioengineering at U of I, in the news release.
“When the virus is held in the NanoGripper’s hand, a fluorescent molecule is triggered to release light when illuminated by an LED or laser,” he said, adding, “When a large number of fluorescent molecules are concentrated upon a single virus, it becomes bright enough in our detection system to count each virus individually.”
More Research and Applications
Gizmodo compared the NanoGripper to a “true Swiss army knife,” able to change and detect other viruses such as HIV and influenza (Flu).
The U of I researchers have already studied the NanoGripper’s ability to detect hepatitis B and plan to publish findings soon, Wang told The Pathologist. He also noted it’s possible the NanoGripper “can be integrated with a lateral flow assay paper strip platform for development of a rapid, sensitive, and inexpensive at home or point-of-care virus detection.”
There is “power in soft nanorobotics,” said Wang, who envisions potential for the NanoGripper beyond viruses to include programming the fingers to detect cancer markers and enabling the grippers to deliver treatment to target cells.
Clinical pathologists and laboratory managers may want to follow this research coming out of the University of Illinois Urbana-Champaign. Once put through additional clinical studies, such nanorobotic diagnostic technology might eventually be used at the point-of-care to help prevent viral infection and spread of disease.
Though they are a mystery, once solved, Obelisks could lead to new biomarkers for clinical laboratory testing
Microbiologists and clinical laboratories know that human microbiota play many important roles in the body. Now, scientists from Stanford University have discovered an entirely new class of “viroid-like” lifeforms residing inside the human body. The researchers detected their presence in both the gut microbiome and saliva samples. Most interesting of all, the researchers are not sure what the lifeforms actually are.
The Stanford researchers, led by PhD student Ivan Zheludev, called the new discovery “Obelisks” due to their RNA structures, which are short and can fold into structures that resemble rods.
The scientists believe the Obelisks went undetected until now in the human microbiome due to their compact genetic elements, which are only around 1,000 characters or nucleotides in size. A typical human DNA structure consists of around three billion nucleotides.
In an article they published on the biology preprint server bioRxiv titled, “Viroid-like Colonists of Human Microbiomes,” the Stanford researchers wrote, “Here, we describe the ‘Obelisks,’ a previously unrecognized class of viroid-like elements that we first identified in human gut metatranscriptomic data. … Obelisks comprise a class of diverse RNAs that have colonized and gone unnoticed in human and global microbiomes.”
The researchers discovered that Obelisks “form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents.”
This is yet another example of how researchers are digging deeper into human biology and finding things never before identified or isolated.
“I am really impressed by the approach. The authors were really creative,” computational biologist Simon Roux, PhD (above) of the Department of Energy (DEO) Joint Genome Institute at Lawrence Berkeley National Laboratory told Science in response to the Stanford researcher’s published findings. “I think this [work] is one more clear indication that we are still exploring the frontiers of this viral universe. This is one of the most exciting parts of being in this field right now. We can see the picture of the long-term evolution of viruses on Earth start to slowly emerge.” How these findings might eventually spark new biomarkers for clinical laboratory testing remains to be seen. (Photo copyright: Berkeley Lab.)
Researchers Bewildered by Obelisks
In their study, “Zheludev and team searched 5.4 million datasets of published genetic sequences and identified almost 30,000 different Obelisks. They appeared in about 10% of the human microbiomes the team examined,” Science reported.
The Stanford researchers found that various types of Obelisks seem to inhabit different areas of the body. In one dataset, the Obelisks were found in half of the oral samples.
The function of Obelisks is unknown, but their discovery is bewildering experts.
Rod-like secondary structures encompassing the entire genome, and
Open reading frames coding for a novel protein superfamily, which the researchers dubbed “Oblins.”
At least half of the genetic material of the Obelisks was taken up by these Oblins. The researchers suspect those proteins may be involved in the replication process of the newly-discovered lifeforms.
The Oblins are also significantly larger than other genetic molecules that live inside cells and they do not have the genes to create protein shells that RNA viruses live within when they are outside of cells.
“Obelisks, therefore, need some kind of host. The researchers managed to identify one: A bacterium called Streptococcus sanguinis that lives mostly in dental plaque in our mouths. Exactly which other hosts obelisks inhabit is yet another mystery, as are what they do to their host and how they spread,” Vice reported.
“While we don’t know the ‘hosts’ of other Obelisks, it is reasonable to assume that at least a fraction may be present in bacteria,” the researchers noted in their bioRxiv paper.
Researchers are Stumped
The Stanford scientists were unable to identify any impact the Obelisks were having on their bacterial hosts—either negative or positive—or determine how they could spread between cells.
“These elements might not even be ‘viral’ in nature and might more closely resemble ‘RNA plasmids,’” they concluded in their paper.
The Stanford scientists are uncertain as to where or what the hosts of the Obelisks are, but they suspect that at least some of them are present in bacteria. However, Obelisks do not appear to be similar to any biological agents that could provide a link between genetic molecules and viruses.
And so, Obelisks are a true mystery—one the Stanford researchers may one day solve. If they do, new biomarkers for clinical laboratory testing may not be far behind.
Leaders in this field are calling these developments “transformative” and say they have the potential to change “all aspects of microbiology.” The driver to this emerging trend is advanced technology that makes it possible to sequence the whole gene sequence of an organism in a day or less, for a cost that is $1,000 and falling rapidly.
In the past six months, microbiologists and pathologists at such hospitals as Methodist Hospital in Houston, Texas, have begun to do whole genome sequencing of microbes found in specimens collected from patients arriving in the emergency room. The New York Times wrote about these developments in a story titled “The New Generation of Microbe Hunters,” that it published on August 29, 2011.
This rapidly-developing threat comes from outside hackers who are launching cyber-attacks aimed at the various medical devices and wireless systems that are directly connected to the Internet and are used by hospitals, physicians, and other healthcare providers. These cyber-attacks demonstrate a new vulnerability that clinical laboratories and pathology groups should recognize.
Use of plasma technology will give healthcare workers another way to clean their hands
Even Buck Rogers and Flash Gordon would be amazed to learn that plasma technology is about to deliver a way for healthcare workers to sanitize their hands without using soap and water! Pathologists and clinical laboratory managers will be interested to learn about a novel device that bathes hands with plasma as a way to reduce the spread of microorganisms by healthcare workers, including superbugs like MRSA, an antibiotic-resistant strain of Staphylococcus aureus.
Prototypes already exist and are designed to be simple for healthcare workers to use. They would simply stick their hands into a small box that bathes the hands with plasma that is specifically engineered to zap bacteria, viruses and fungi. The plasma used in the hand sanitizer is a gas similar to that used in fluorescent lights, neon signs, and televisions, but works at room temperature and pressure.
