Архив рубрики ‘ Nanotechnology against COVID19

Building mRNA vaccines for COVID19

Building mRNA vaccines for COVID-19
Coronaviruses invade cells through surface molecules called spike proteins (named for the fact that they physically jut out from the rest of the virus), which take on different shapes in different coronaviruses. The SARS-CoV-2 specific spike protein is therefore a crucial antigen – i.e. a substance that induces the immune system to produce antibodies against it – that can be exploited for vaccine design.
And this is how an mRNA vaccine against COVID-19 works: Once the virus genome is sequenced – that means it is available as a digital copy – researchers can design an mRNA sequence that encodes the blueprint for the virus spike protein. Once tested for efficacy and safety in clinical trials, the mRNA molecule can then be synthesized on an industrial scale in robotic factories.
This mRNA molecule is wrapped with a lipid nanoparticle envelope, which protects it from degradation, and then directly delivered into cells. There, ribosomes get to work and read the mRNA as just any other blueprint – only this time they synthesize the spike protein. The finished spike proteins are then attached to the surface of cells where they are recognized by the immune system, eventually triggering the desired immune response against the virus.In other words: Once you get your vaccine jab, the genetic instructions contained in the mRNA molecules are injected into the upper arm and the ribosomes in the muscle cells translate them to make a critical fragment of the viral protein directly inside your body. This 'preview' of what the real virus looks like gives the immune system time to design powerful antibodies that can neutralize the real virus if it ever gets in contact with it.The protein production inside the muscle cells initiated by the injected mRNA injection reaches peak levels for 24 to 48 hours and can last for a few more days. Thereafter, the mRNA molecules get disassembled by the body.

The revolutionary impact of mRNA technology

mRNA COVID-19 vaccines have demonstrated in a very convincing way that biotechnologies have entered the industrial age. What we are seeing here is nothing less than the rise of bio platforms that give us the ability to engineer bits of biology, such as mRNA, to create programmable medicines and vaccines.

More generally, if it is indeed possible that mRNA can be used to make the full set of proteins in life, then it becomes possible to treat an incredible broad range of human diseases. This is at the core of the industrialized platforms that Moderna, BioNTech and others are building.

Essentially, an mRNA technology platform functions very much like an operating system on a computer. It is designed so that it can plug and play interchangeably with different programs. In this case, the 'program' or 'app' is the unique mRNA sequence that codes for a specific protein.

mRNA as the technological basis for therapeutics and vaccines is characterized by a great flexibility with respect to production and application. In essence, mRNA is an information-carrying molecule that can be industrialized – as opposed to traditional therapeutic molecules that have to be elaborately designed and synthesized from scratch for each application (i.e. medicine).

For starters, mRNA molecules are far simpler than proteins. mRNA is manufactured by chemical rather than biological synthesis, so it is much quicker than conventional vaccines to be redesigned, scaled up and mass-produced.

An excellent primer on the development of mRNA-vaccine technologies explains why: «Any protein can be encoded and expressed by mRNA, in principle enabling the development of prophylactic and therapeutic vaccines fighting diseases as diverse as infections and cancer as well as protein replacement therapies.»

And this is very the disruptive effect of the mRNA platform happens: If a therapy requires a certain protein to be encoded, only the sequence of the messenger RNA molecule needs to be changed, leaving its physicochemical characteristics largely unaffected. In the above computer analogy, that is like writing a new piece of software that runs on the same operating system.

The disruptive force of emerging bio platforms

This means that diverse products can be manufactured using the same established production

process – the same equipment, the same operators – without any adjustment and thereby saving massive amounts of time and money compared with other vaccine or therapeutics platforms. Читать запись полностью »

Role of nanotechnology in the race to find a Covid-19 vaccine

Today I would like to acquaint readers of my blog with a summary of the data published on the site Nanowerk about the role of nanotechnology in the race for the Covid-19 vaccine.

Nicole Steinmetz, professor of nanoengineering at UC San Diego and corresponding author on the study, spoke with Nanowerk about the findings in this paper. Steinmetz believes “it is an exciting time for nanotechnology and nanoparticle delivery of nucleic acid-based vaccines and subunit vaccines are poised to make an impact.”

The COVID-19 pandemic has left the world reeling following its inception in Wuhan, China. While global efforts are being directed towards a vaccine, thus far none have passed the trial stage. Until humanity achieves herd immunity to this virus, either through exposure and infection or through inoculation, there can be little hope of our returning to our pre-COVID-19 life.

Fortunately, there are over two hundred academic laboratories and companies around the world searching for a vaccine, and the pace at which they are progressing is unprecedented. One nanotechnology formulation achieved clinical trials a month prior to other conventional approaches. However, due to the stiff regulatory requirements on vaccines to ensure safety, there remain various hurdles that companies must surmount in order to establish a viable vaccine.

Nanotechnological approaches have received a boost despite their lack of clinical trials. As an example, mRNA vaccines have been developing for thirty years but were not previously approved. Due to the adaptability of such technology, prior vaccine candidates can be repurposed using previously developed nanostructures.

Nanoparticles and viruses operate on the same scale, and thus there are various nanotechnological aides which are being used in the development of potential vaccines. Nanoparticles are capable of entering the cell through biological channels, and can deliver antigens there. Antigens are typically delivered via either lipid nanoparticles (LNPs), which encapsulate the antigens, or via other benign viruses including Ads.

Due to the scale of nanoparticles, they are capable of traveling in vivo differently than other molecules. The lymphatic system, which is critical in orchestrating immune responses, has typically proved challenging to access. However, with the advent of nanoparticles, previously inaccessible pathways have become accessible, with certain trial vaccines attempting to use these to transport antigens.

Besides delivering antigens themselves, nanoparticles can also be enlisted to provide adjuvants to cells. Adjuvants effectively catalyze the immune response, allowing the cell to more easily recognize and respond to antigens. Encapsulating both the antigen and adjuvant in the same envelope provides for better-targeted delivery and response from the cell.

The presence of adjuvants may also reduce the amount of antigen required to engender a response, and thus render a dose-sparing effect. This dose-sparing may drive the cost of immunization down, and render wide-spread inoculations more feasible. Without co-delivery of adjuvants and antigens, antigens are more likely to break down in the body. Читать запись полностью »

Nanostructured surface inactivates SARS-CoV-2 coronavirus within six hours

While the number of bacterial and viral infections has been steadily rising, the emergence of the novel Covid-19 pandemic has caused a surging demand for antimicrobial treatments that can keep surfaces clean, particularly in health care settings. However, all of these surfaces and coatings have been developed to combat bacteria but not to kill off viruses.

Quite surprisingly, so far the effect of nanostructured surfaces on viruses has never been investigated.

In new work reported in ACS Biomaterials Science & Engineering («Antiviral Nanostructured Surfaces Reduce the Viability of SARS-CoV-2»), researchers from the Centre for Biomedical Technologies at Queensland University of Technology have successfully produced durable antiviral surfaces that inactivate SARS-CoV-2 within 6 hours.

In contrast, on various non-nanostructured surfaces or smooth surfaces, the SARS-COV-2 virus remained viable for up to 48 hours.

«Our results provide evidence that surfaces that are structured with specific nanoscale surface features are effective in preventing SARS-CoV-2 and the subsequent environmental spread,» Jafar Hasan, the paper's first author, tells Nanowerk. «Such nanostructured surfaces can be used in hospital environments such as trolleys, bed-rails, door-knobs, etc. These surfaces can be extended to other industrial sectors and public infrastructure such as transportation, where fomites or contaminated surfaces are carriers for viral infections.»

This research has grown out of earlier work (ACS Biomaterials Science & Engineering, «Antiviral and Antibacterial Nanostructured Surfaces with Excellent Mechanical Properties for Hospital Applications») where the team, led by Prof. Prasad K.D.V. Yarlagadda, showed that nanoscale topography can kill and inactivate a wide range of bacteria and viruses. Читать запись полностью »

Combatting COVID-19 at the nano level

Today I bring to your attention a very recent report on the application of nanotechnology for the manufacture of masks against COVID-19. I want to share new interesting data with my readers, so I am giving a message completely without any changes. The message has a title “Combatting COVID-19 at the nano level”. It was published in the Nanowerk News.

Copper, a metal commonly used throughout history for its antibacterial properties, is being utilized by researchers at IUPUI’s Integrated Nanosystems Development Institute to solve a problem very relevant today: making reusable face masks safer and more comfortable for daily use.

“We wondered how we could use our existing technology to turn something used in ancient times, like copper, into protection against COVID-19,” said Mangilal Agarwal, director of the Integrated Nanosystems Development Institute and professor of mechanical and energy engineering. “Any virus sitting on the surface that comes in contact with copper will be killed because of the antiviral properties.”

Agarwal and Hamid Dalir, associate professor, are applying a patented technology developed at IUPUI to manufacture reusable face masks using copper, a metal often used in the production of high-touch objects like doorknobs and handles. Their goal is to improve filter performance by trapping and disabling airborne virus particles.

“These masks have copper oxide applied at the nano level and would offer ultimate protection against virus risks like COVID-19,” Agarwal said. “Some cloth masks allow the small airborne particles to pass through, but with our technology, it would be close to 100% proof that you have the capability incorporated in the mask to deactivate the virus and improve filter performance.”

The technology – initially developed at IUPUI to make composite materials cheaper, lighter and stronger using nanomaterials – could be used to coat household masks with a layer of fabric protection inlaid with copper nanoparticles that disable virus particles as they reach the surface. The general public would be able to wear a reusable mask that offers the same superior level of protection as masks worn by healthcare providers, such as N95 masks.

“To make any fabric into a mask or filter, we have to provide the nanostructure, and we can put that nanostructure on a roll-to-roll printing machine with the fibers at nanoscale,” Agarwal said. “We are using electrospinning, using the electric field to spray the nanofibers onto the fabric.”

Agarwal and Dalir disclosed their technology to the Indiana University Innovation and Commercialization Office, and are looking to commercialize it through their startup. They plan to work with local companies manufacturing COVID-19 supplies under the Defense Protection Act.

Beyond face masks, the technology can be applied to other methods for fighting COVID-19, such as HEPA filters found in HVAC systems. Without good filters, Agarwal said, airborne virus particles could circulate between indoor areas. By applying the copper material to the filters, there could be virus free air circulation in buildings and hospitals.

“Our technology is good for masks and filters because we are not changing the manufacturing process,” Dalir said. “We just get the rolls of the mask and filter, manufacture and enhance it with copper-coated fabric and then use it as it would be used conventionally.”

Their company, Multiscale Integrated Technology Solutions, was recently selected as one of five Hoosier startup winners of the Elevate Nexus Statewide Pitch Competition, a program designed to support Indiana startups.

“Elevate Nexus is being funded by a grant from the U.S. Economic Development Administration and the 21st Century Research and Technology Fund to help startups that have shown potential for commercialization to get connected with entrepreneurs to build on existing operational strategies," Dalir said. "What we're trying to do is raise the existing entrepreneurship support vehicles as well as attract investment in our startup at an earlier level so that we can have the opportunity to further grow and cultivate new investors as we de-risk our venture.”

The commercialization of their technology has the potential to greatly impact lives here in Indiana and around the world – providing a safe solution against the spread of COVID-19.