Guillermo U. Ruiz-Esparza

A beacon of hope in the fight against the pandemic, mRNA vaccines have been utilized to immunize millions of citizens around the world for protection against the COVID-19 virus. The development of these vaccines would not have been possible without decades of research and progress in the fields of nanotechnology and biotechnology. Nanotechnology researchers work on the nanoscale—employing specialized lipid shell nanoparticles to deliver the delicate mRNA vaccine sequence to specific cells.

Guillermo U. Ruiz-Esparza, MD, PhD, FRSA, is a physician-scientist and is an expert in the field of nanomedicine. He also  part of the Divisions of Engineering in Medicine and Renal Medicine at the Brigham and Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology. Ruiz-Esparza, who is focused on developing nanotechnology-based therapeutics, diagnostics, and tissue engineering technologies, sat down with CRN to talk about his recently published paper in the scientific journal Nano-Micro Letters about the role of nanotechnology during the COVID-19 pandemic, and the extensive, developmental process of generating nanotech-enabled mRNA vaccines.

What motivated you and your team to write this paper?

GURE: Innovation is found at the intersection of different fields or disciplines, and it was certainly an innovative time when the fields of nanotechnology and mRNA research were combined to combat the COVID-19 pandemic. I was impressed by the speed with which researchers understood the ability of these technologies to profoundly impact human health and in turn employ them in the critical development of both the Moderna and Pfizer vaccines. Interestingly, the Pfizer vaccine is the first ever mRNA vaccine for human use to recently receive full approval from the Food and Drug Administration (FDA). With heightened interest in understanding the role of nanotechnology during the COVID-19 pandemic, I felt it was important to collaborate with a group of multidisciplinary scientists and physicians from the Harvard Medical School, Harvard T.H. Chan School of Public Health, MIT and Tecnologico de Monterrey to study and comprehensively review the nanotechnology-based mRNA developmental process from the preclinical phase to the approval stage, the regulatory pathway encountered, lessons learned as well as the manufacturing hurdles faced.

How did nanotechnology enable the development of vaccines in response to the COVID-19 crisis?

GURE: When translating mRNA technology to patients, significant delivery challenges were encountered. We often wondered how we could deliver the mRNA to the human body in a targeted, stable fashion given that it is highly unstable and rapidly degrades without a suitable vector. Nanotechnology resolved many of our concerns by enabling efficient mRNA encapsulation and delivery into specific cells without degradation. Upon entering to our cells, facilitated by a nanoparticle, mRNA is translated into the non-disease-causing SARS-CoV-2 spike protein, a key component of viral pathogenesis. Our immune system then mounts an immune response against the foreign spike protein, creates memory cells to recognize the protein, and provides us with immunity.

Prior to COVID-19, how was nanotechnology used?

GURE: Even if it was not called by its modern name, the first users of nanotechnology were several ancient civilizations. The Egyptians leveraged nanotechnology to infuse beautiful colors into their art and cosmetics, Romans to craft iridescent glassware, and Damascans to create swords with exceptionally sharp edges. In modern times, scientists Richard Feynman, Norio Taniguchi and Eric Drexler popularized and defined a lot of what we now know about nanotechnology. In medicine, nanotechnology, commonly referred to as nanomedicine, has had a profound impact on cancer treatment. The FDA has approved a variety of chemotherapies that utilize nanoparticle-based systems, such as Abraxane and Doxil, to treat several types of cancer. Other medical disciplines such as surgery, dermatology, ophthalmology, and cardiology are already employing nanotechnology or in the process of rapidly adopting it as well.

What is one of the biggest limitations of mRNA-based, nanotechnology-enabled vaccines?

GURE: With every medical invention, there are certainly some disadvantages that we must consider. Though the nanoparticles prevent mRNA enzymatic degradation and enable efficient intracellular delivery, the strict temperature requirements for the Pfizer and Moderna vaccines often contribute to the challenges other countries face in distributing, promoting, and rapidly vaccinating their citizens. Additionally, the start of the pandemic was marked by difficulties in balancing vaccine supply and demand.

What are your thoughts on the rise of new SARS-CoV-2 (COVID-19) variants?

GURE: The variants will continue to appear and since there are still large numbers of unvaccinated citizens, SARS-CoV-2 has an increased opportunity to mutate. Thankfully, the advantage of using nanotechnology-enabled mRNA vaccines is that much like computer code, researchers can quickly modify or update the genetic sequence of the vaccine in a scalable manner. By doing so, researchers can now improve or enable the immunological recognition of new variants, provide boosters, and ensure that every individual can better protect themselves and their loved ones.

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