A groundbreaking nanorobot, resembling a four-fingered hand and engineered from a single DNA strand, has the ability not only to trap the virus responsible for Covid-19 but also to prevent viral particles from entering host cells. This innovation could revolutionise future virology.
The first model of a nanorobot – widely recognised as a pioneering invention – was a glucose-powered device the size of a human hair, created in 2004 by a team at the University of California, Los Angeles. Its movement was driven by a nanoscale fragment of rat cardiac muscle, enabling it to travel at a speed of 40 micrometres per second, where one micrometre (µm) equals one-thousandth of a millimetre.
Since then, research has explored – and continues to explore – the feasibility of nanoscale robotic systemsdriven by magnetic fields, electric fields, or external light stimuli, constructed from nanoparticles, biological molecules, or DNA strands.
Among these materials, DNA stands out due to its unique properties: its biomolecules are capable of self-assembling and, once their task is complete, degrading naturally within the body, eliminating toxicity risks. These attributes make DNA particularly suited to future diagnostic and therapeutic applications, which are a cornerstone of nanorobotics. Such applications demand nanorobots that can navigate fluidly through all kinds of interstitial spaces, tissues, and bodily fluids, performing tasks such as inspecting structures, delivering drugs, attacking tumours, repairing or replacing organelles, and dissolving clots.
Unlike the earliest nanorobots, which featured tiny legs powered by rat cardiac muscle cells and moved via mechanical joints, DNA-based nanostructures are more efficient, biocompatible, and safer for human health.
TAKEAWAYS
DNA-based nanorobots with gripping functions
Since the onset of the pandemic, research efforts have increasingly focused on designing DNA-based nanorobots capable of detecting and/or blocking viruses within the body. However, these efforts have encountered a significant obstacle: the lack of dexterity required to grasp individual viral particles effectively.
A notable recent study (2023), led by the Nanjing University of Posts and Telecommunications in China and published in “Recent Advances in DNA Nanotechnology-Enabled Biosensors for Virus Detection” (Biosensors), highlights the challenges faced by this emerging field. Key issues include the need for a deeper understanding of the relationship between the geometry of DNA nanostructures and their performance, as well as improving the static stability of these designs.
«The ongoing pursuit of advancements in this specific area promises to revolutionise current diagnostic and therapeutic tools – the authors note – paving the way for more accurate and personalised approaches to healthcare».
One innovative response to these challenges comes from a team of scientists at the University of Illinois Urbana-Champaign (USA). In their paper, “Bioinspired Designer DNA NanoGripper for Virus Sensing and Potential Inhibition” (Science Robotics, November 2024), they describe the development of a hand-shaped DNA nano-gripper inspired by the human hand and the talons of birds.
«The design features a robotic nanodevice equipped with four foldable fingers and a palm. Each finger mimics the mechanics of human fingers, consisting of three joints that enable bending. The degree of flexibility is determined by the underlying design of the DNA scaffold».
In essence, each “finger” of the hand-shaped nano-gripper is composed of three phalanges connected by three rotating and flexible joints. These functions are facilitated by interactions between the fingers and their binding components, made from DNA, a biocompatible and versatile material.
What is the “DNA Origami” technique?
Beyond its biocompatibility and versatility, the research team employed DNA for its structural properties, including strength, flexibility, softness, programmability, and addressability. These unique features enable the nanomachine to perform unprecedented gripping actions, allowing it to interact with cells, viruses, and other molecules within the human body.
The underlying method is known as “DNA Origami.” The researchers clarify, however, that «even in the context of this technique, our approach is innovative in terms of design principles. We fold a single, long DNA strand back and forth to create all components, both static and movable, in a single step».
DNA Origami, where the term “Origami” refers to the Japanese art of folding paper to create arbitrary shapes and dimensions, is one of the most advanced techniques in nanotechnology applied to nanomedicine. The method involves «long DNA strands – 200–300 nucleotides – folded into a complex scaffold, which in turn forms a nanoscale structure». This approach has shown (albeit still in experimental stages) remarkable precision and efficacy in cancer diagnostics and therapies aimed at combating the disease [source: “DNA Origami” – Science Direct].
The first microscopic images of DNA Origami, and the official coining of the term, were presented in a groundbreaking article published in Nature in 2006, titled “Folding DNA to Create Nanoscale Shapes and Patterns.”
Drawing inspiration from this ancient Japanese art, researchers at the University of Illinois Urbana-Champaign have developed self-assembling DNA nanocages capable of capturing even large viruses. Let us explore how this works.
Nanorobots binding to molecular targets: the example of the SARS-CoV-2 virus
The four-fingered hand-shaped nanogripper – scientists explain – has been paired with a photonic crystal sensor platform. From this combination, a diagnostic test for COVID-19 has been developed, matching the sensitivity of molecular tests currently used in hospitals worldwide.
How does the nanosystem work? The nanorobots created behave as highly sensitive biosensors, capable of selectively detecting the SARS-CoV-2 virus in human saliva, with a detection limit of approximately 100 copies per millilitre.
The fingers of the virus-capturing hand contain regions called “DNA aptamers,” specifically programmed to bind to molecular targets, such as the spike protein in the case of the COVID-19 virus. This mechanism causes the fingers to flex and wrap around the target, effectively capturing it.
On the opposite side, where the “wrist” of the hand-shaped nanorobot is located, the nanomachine can adhere to another nanostructure, for example, one designed for drug delivery.
«During the experiments – the team adds – we discovered that when our nanorobots were introduced into cell cultures exposed to SARS-CoV-2, multiple hands began to wrap around the outside of the viruses. This action blocked the interaction between the viral protein (the spike, to be precise) and the receptors on the cell surface, thus preventing infection».
Let us now attempt to analyse the significance of this tool as a preventative therapy against infections of various origins.
Glimpses of Futures
The design of self-assembling nanomachines, created using a specific DNA Origami technique (folding a single DNA strand back and forth), points to a potential pathway in the coming years for nanomedicine solutions aimed at detecting and potentially inhibiting viral infections.
To anticipate possible future scenarios, let us outline – using the STEPS matrix – the multifaceted impact that the development of the described nanorobot model might have.
S – SOCIAL: researchers at the US university have demonstrated through in vitro laboratory experiments that their virus-capturing hand-shaped nanorobots can effectively block the entry of coronavirus into host cells. This raises the prospect of their future use as a preventative therapy. For instance, an antiviral nasal spray composed of four-fingered nanogrippers could be developed to prevent various types of inhaled viruses – not only COVID but also influenza and other respiratory viruses – from interacting with nasal cells and penetrating the body to cause infection. Furthermore, as the nanorobotic hand evolves, it could one day be programmed to identify a range of markers (including tumour markers) present on the surface of cells, and to facilitate targeted drug delivery, such as transporting anticancer treatments directly to target cells.
T – TECHNOLOGICAL: in the future, the evolution of the initial hand-shaped nanogripper model will likely necessitate modifications to its three-dimensional structure to further enhance stability and grip. This could lead to a departure from the commonly used DNA Origami technique, which relies on multiple DNA strands, both long and short. Instead, the choice to employ a single long DNA strand to create all components in a single step – optimising dexterity for capturing individual virus particles – may be replaced by alternative nanostructure design methodologies. Such adaptations would be necessary to tailor the nanorobots to different viruses and varied viral detection and inhibition requirements.
E – ECONOMIC: envisioning a future where advancements in nanorobotics applied to viral infection prevention allow for the use of a simple nasal spray or tablet containing DNA-based nanomachines at the first signs of illness – or during periods of high contagion risk – it is reasonable to anticipate a significant reduction in national healthcare spending. These nanomachines could immediately detect and capture viruses, preventing their entry into host cells. For example, in Italy alone, the AIFA (Italian Medicines Agency) reported in its 2023 National Report, published in September 2024, that last year the public expenditure on antivirals amounted to €619.2 million, an increase of 0.9% compared to 2022. With the adoption of such nanotechnological solutions, the costs associated with antivirals, flu medications, and related treatments such as antipyretics and anti-inflammatories could be drastically reduced.
P – POLITICAL: nanomedicine that leverages nanorobotics to achieve breakthroughs in areas like virology – a field still underexplored in the application of emerging technologies – presents a challenging regulatory landscape, particularly for European Union countries. The future adoption of nanorobots as inhibitors of viral infections would raise several questions regarding their safety for human health. These concerns would not stem from the materials used in their construction or the recovery techniques post-injection or ingestion (these are DNA-based nanostructures, biodegradable within the body) but rather from their interactions with human tissues and fluids, as well as the potential long-term consequences of their use. In this context, a future scenario would require a comprehensive legislative framework to regulate these aspects and a dedicated supervisory commission to conduct periodic inspections.
S – SUSTAINABILITY: the adoption of future preventative therapies against infections of various origins, relying not on conventional drugs but on DNA-based nanorobots (which are non-toxic) equipped with virus-capturing “hands” that block interaction with cell surface receptors upon inhalation, would lead to a drastic reduction in the use of chemical antivirals. This shift would have positive downstream effects, including a lower risk of pharmaceutical waste dispersal and improved wastewater treatment outcomes, contributing to greater sustainability in both healthcare and environmental sectors.