Mª José Alonso’s pioneering contribution to nanomedicine and RNA vaccines

As part of the launch of the report Neurotechnology for human well-being, the Bankinter Innovation Foundation continues with the informative work through a new webinar. The report is the result of the meeting of our think tank Future Trends Forum, where we convened more than 40 internationally renowned experts to discuss the repair and enhancement of human capabilities through neurotechnology and other innovative applications, and to analyse the opportunities and risks that arise.

In this new webinar, Advances in Messenger RNA Vaccines, we have had the privilege of having the expert María José Alonso, a pioneering world figure in the field of nanomedicine and messenger RNA vaccines. His career, marked by stays in prestigious international institutions and recognitions such as the Juan de la Cierva National Research Award, the Medal of Merit in Research and University Education and the Jaume I Award for New Technologies, underlines the importance of his contribution to the advancement of pharmaceutical science and technology.

María José Alonso is Professor of Pharmacy and Pharmaceutical Technology at the University of Santiago de Compostela. He has worked at the University of Paris-Sud, the University of Angers and the Massachusetts Institute of Technology (MIT). His laboratory has been a pioneer in Spain in nanomedicine, having participated in international consortia funded by the World Health Organization, the Bill and Melinda Gates Foundation and the American Health Institute, as well as the Canadian Health Institute and the European Commission. She is the author of more than 230 scientific contributions with more than 11,500 citations and the inventor of 18 patent families. Due to the quality of its work, it has been among the TOP TEN in Pharmacology ( Times Higher Education international ranking). He is also a member of the editorial board of 10 specialized journals.

Here you can watch the webinar with María José Alonso:

Advances in messenger RNA vaccines with MªJosé Alonso

Below, we summarize the key ideas and discoveries that María José shared during this webinar:

A journey from the pandemic to the present

The COVID-19 pandemic, an unprecedented event in recent history, brought with it colossal challenges for humanity. In this context of uncertainty and urgent need, messenger RNA vaccines emerged as a beacon of hope, ushering in a new era in vaccine science and therapeutics.

When SARS-CoV-2 burst onto the scene, the world was largely unprepared to face a crisis of such magnitude. However, science did not start from scratch; decades of research into messenger RNA and nanomedicine technologies provided the foundation upon which effective COVID-19 vaccines could be rapidly developed. Unprecedented collaboration between academics, industry, and governments accelerated this process, demonstrating the ability of the global community to come together in the face of a common threat.

Beyond their efficacy in the fight against COVID-19, messenger RNA vaccines have proven to be a versatile and powerful platform for the development of future vaccines and therapeutics. Technology allows rapid adaptation to new pathogens, an extraordinary feature in a world where emerging diseases represent a constant threat. In addition, their ability to be reprogrammed offers a path to personalized vaccines, opening up a range of possibilities in preventive and curative medicine.

The rapid rollout of messenger RNA vaccines has also had a profound impact on public perception of vaccines and modern medicine. Although vaccines have historically been one of the most significant medical advances, the COVID-19 emergency and the effective vaccine response have reinforced their value in the collective consciousness. This recognition of the importance of vaccines is critical to addressing future health crises and to maintaining public health in the long term. Despite the advances, the journey has not been without its challenges. Skepticism in certain sectors of the population underscores the need for clear and accessible scientific communication. In addition, the equitable distribution of vaccines remains a global challenge, emphasizing the importance of international solidarity and access to health as a universal human right.

The legacy of messenger RNA vaccines goes beyond their contribution to the containment of the COVID-19 pandemic. We are witnessing the birth of a revolution in gene therapy and personalized medicine, with potential that we are only beginning to explore. Diseases that were once considered untreatable are now in the crosshairs of these innovative therapeutic strategies. Research and development in this field promises to transform our approach to preventing, treating, and ultimately curing complex diseases.

The journey from the pandemic to the present, led by visionaries such as María José Alonso, has changed the trajectory of modern medicine and redefined our relationship with science and health. As we venture into this promising future, collaboration, innovation, and commitment to health equity must guide our steps. The story of messenger RNA vaccines is a testament to what we can achieve together, and it is a hopeful omen of what is to come.

The messenger RNA revolution

The messenger RNA (mRNA) revolution represents one of the most significant advances in the history of medicine, promising to transform the way we fight viruses and infectious diseases and also how we tackle genetic disorders, chronic diseases and cancer.

Fundamental principles of mRNA: mRNA technology is based on the use of synthetic messenger RNA sequences to instruct the cells of the human body on how to produce specific proteins that trigger an immune response or induce a therapeutic effect. This approach harnesses the natural mechanism of cells to generate proteins, offering unprecedented flexibility and efficiency in the design of vaccines and therapeutics. mRNA COVID-19 vaccines have proven to be a triumph of science and innovation, offering outstanding efficacy with a robust safety profile. However, the impact of this technology goes beyond the pandemic. The ability to rapidly design vaccines against new pathogens could fundamentally change our response to future public health emergencies, while the adaptability of the mRNA platform opens the door to vaccines against a wide range of diseases, from influenza to Zika.

Beyond vaccines: gene therapies and more: the potential of mRNA technology extends far beyond vaccines. Gene therapy, regenerative medicine, and cancer treatment are just a few of the fields that could benefit from this revolution. For example, mRNA can be designed to restore the expression of defective or absent proteins in genetic diseases, offer new strategies to repair damaged tissues, or program the immune system to attack cancer cells.

Despite their enormous potential, the widespread implementation of mRNA-based therapies faces technical and logistical challenges, including the stability of mRNA molecules and efficient delivery to target cells. Nanotechnology, especially the use of lipid nanoparticles , has emerged as a promising solution, enabling the effective protection and delivery of mRNA within the body. Looking ahead, continued research and development is essential to overcome the remaining obstacles and unlock the full potential of mRNA therapies. The mRNA revolution is just in its infancy, but it has already changed the way we think about vaccines and medical therapies.

The role of nanoparticles

The messenger RNA (mRNA) vaccine revolution could not have materialized without the parallel development and integration of an equally innovative technology: nanoparticles. These microscopic structures have proven to be instrumental in the efficacy and delivery of mRNA-based therapies, representing a crucial advance in medicine and pharmacology. The contribution of experts such as María José Alonso in the exploration and application of nanoparticles in nanomedicine has been fundamental, allowing us to enter new frontiers of medical science.

The nanoparticles used in mRNA vaccines are mostly lipid nanoparticles. These structures are designed to encapsulate and protect the delicate mRNA from degradation before it can be delivered to the body’s cells. Once inside the cell, the nanoparticles release the mRNA, allowing the protein translation process to take its natural course. This functionality solves one of the most significant challenges in the development of mRNA vaccines: the efficient and safe delivery of genetic material into cells without being destroyed by the body’s defense mechanisms. The use of nanoparticles has revolutionized both the delivery of mRNA vaccines and the delivery of a wide variety of therapies. Its ability to cross biological barriers, such as the blood-brain barrier, opens up new possibilities for treating previously unattainable diseases. In addition, the surface modification of these nanoparticles allows for specific steerability, meaning they can be designed to target specific cell types, improving the efficacy of the therapy and minimizing side effects.

One of the most critical aspects in the development of nanoparticles is to ensure their safety and biocompatibility. Research in this field focuses on understanding how these particles interact with the human body at the cellular and molecular level. Advances in nanotechnology have allowed the design of nanoparticles that are effective in their function and also safe, with a degradation and elimination profile suitable for use in humans.

The application of nanoparticles in medicine extends beyond mRNA vaccines. From targeted drug delivery to gene therapy to tissue engineering, the possibilities are enormous. Continued research in this field promises to develop new generations of nanoparticles with even more specific and efficient capabilities, potentially revolutionizing the treatment of complex diseases, including several types of cancer and genetic disorders.

Advanced therapies

Advanced therapies, characterized by their innovative and personalized approach, are ushering in a new era in disease treatment. These therapies, which include drugs based on genes, cells and tissues, represent a fundamental transformation in our approach to medicine, promising more effective and personalized treatments for a wide range of conditions. Gene and cell therapy offers unprecedented hope for patients with previously untreatable diseases, including rare genetic disorders, certain forms of cancer, and degenerative diseases. By modifying the genetic material within the patient’s cells or providing new cells to replace dysfunctional ones, these therapies can offer long-term solutions, and in some cases, potential cures.

Nanomedicine, a pioneering field in which María José Alonso has made significant contributions, plays a crucial role in the development of advanced therapies. Nanoparticles can be designed to deliver gene and molecular therapies directly to target cells or tissues, improving the efficacy of treatments and minimizing side effects. This precision is unprecedented in conventional medicine and opens up new possibilities for highly personalized and less invasive treatments.

Despite the transformative potential of advanced therapies, they face significant challenges, from technical and scientific issues to ethical and regulatory considerations. The large-scale production of gene and cell therapies, ensuring their safety and efficacy, and equitable access to these advanced treatments are critical areas that require ongoing attention and innovative solutions.

Proteins are responsible for health

Proteins, fundamental in cell biology and human health, are produced from instructions encoded by messenger RNA. This understanding has led to the development of vaccines and therapies that, through the administration of synthetic messenger RNA, enable our body to fight diseases at their source, without altering DNA or permanently integrating into our genome.

The speed with which COVID-19 vaccines were developed was not an accident, but the result of decades of accumulated research in fields such as nanotechnology, artificial intelligence, genomics, and proteomics. The combination of these technologies allowed significant advances in medicine, with lipid nanoparticles standing out as crucial vehicles for the safe and efficient transport of messenger RNA within the body. The contribution of scientists such as Nobel laureates Drew Weissman and Katalin Karikó, Robert Langer and Peter Cullis has been fundamental in the development of lipid nanoparticles and the modification of messenger RNA for stability and lower immunogenicity. These innovations have paved the way for treatments of genetic, autoimmune, neurodegenerative diseases and, especially, cancer, using both therapeutic vaccines and interfering RNA to target disease-causing proteins.

Companies like Moderna, backed by decades of research and development, are leading the expansion of these therapies, addressing a variety of infectious and chronic diseases. Moderna’s momentum and success, especially during the COVID-19 pandemic, demonstrates the transformative potential of these technologies in medicine.

Innovation continues through projects such as NOSE VAC, which explore alternative routes of administration, such as nasal delivery, to facilitate vaccination globally, especially in regions with limited access to medical infrastructure. In addition, the research extends to the transport of genetic material to the brain to treat diseases such as Alzheimer’s, demonstrating the potential of messenger RNA and nanoparticle-based therapies to revolutionize the treatment of complex diseases.

The future: precision medicine

The conclusion of María José Alonso’s presentation highlights the crucial role of precision or personalized medicine, especially in the treatment of cancer. This approach focuses on using an individual’s genomic information to develop specific treatments that address the molecular causes of the disease. A prominent example is work on correcting specific mutations in the KRAS protein, which is responsible for several types of severe cancers. Precise intervention on these mutations opens up new avenues for treating pancreatic, colorectal, and lung cancers through personalized therapies. The relevance of nanoparticles in this context is vital. They act as effective vehicles for delivering gene therapies and biologics directly to affected cells, overcoming the cellular barriers that traditionally limit the efficacy of many treatments. Nanoparticles allow, for example, treatments targeting the mutated KRAS protein to penetrate the cell membrane and reach their target with precision, demonstrating significant tumor reductions in experimental models.

Notable people in the scientific field, such as Drew Weissman and Nobel laureates such as Jennifer Doudna, have recognized the importance of nanoparticles for the development of vaccines, such as those from Moderna and Pfizer, and also as revolutionary tools for the treatment of diseases. Doudna highlights the need for nanoparticles to effectively direct gene-editing tools like CRISPR-Cas9 toward their specific targets.

To conclude, María José Alonso tells us: “At the recent presentation of the 2023 National Research Awards, our king expressed it clearly: without science, there is no future. And hopefully there will be an increasingly strong commitment to science in Spain, because without science there is no future, and therefore there will be no future for Spain“.

Q with María José Alonso

After the presentation, María José Alonso answers some of the many questions from the audience. Below is a summary of them:

How is messenger RNA designed and synthesized for encapsulation?

The synthesis of messenger RNA is a relatively simple process, carried out by biotechnologists, which involves the chemical modification of RNA. Although María José Alonso is not an expert in the manufacture of mRNA, she highlights the simplicity of its production, evidenced by the development of mRNA vaccine factories in African countries. The main challenge lies in the design of nucleotide sequences and their chemical modifications.

Are patients being stratified to administer vaccines?

Infectious vaccines are usually given to the entire population, while precision medicine for diseases such as cancer does require stratification. Alonso suggests that while he personally hasn’t had problems with multiple vaccinations, stratification, especially by age, could improve accuracy in vaccine administration.

What is your opinion on the use of AI in drug development?

María José Alonso positively values the use of Artificial Intelligence in the development of medicines, highlighting its transformative role both in diagnosis and in the creation of new drugs. He specifically mentions César de la Fuente’s work at the University of Pennsylvania, especially his focus on the production of antibiotics using AI, underscoring the importance and potential of this technology to revolutionize the field. Alonso highlights collaboration on vaccine projects in Spain, where AI was crucial in exploring nucleotide combinations, anticipating a greater impact in areas such as nanomedicine.

Does this technology detect specific mutations?

Yes, nanoparticles could be used to detect abnormalities in diseases such as glioblastoma through early diagnosis, using monoclonals to identify abnormal proteins as part of a screening strategy.

What are the biggest challenges for nasal vaccine development?

Challenges include the form of administration and the need to prove that nanoparticles do not reach the brain through the olfactory epithelium. However, nasal administration looks promising because of its direct access to the immune system associated with the nasal mucosa.

Who controls patents on messenger RNA vaccines?

There is competition among pharmaceutical companies for patents related to mRNA, nanoparticles and other components of vaccines. Although patents are fundamental in the industry, litigation frequently arises, especially when marketing new products. Alonso mentions the effort made by his team to develop a COVID-19 vaccine with a different composition than Moderna’s to avoid patent infringements.

If you couldn’t see it, you can watch the webinar here:

Advances in messenger RNA vaccines with MªJosé Alonso

If you want to delve deeper into this field and other technologies and innovations for human well-being, be sure to check out our report.

You can also access other webinars on the subject:

• Neurotechnology for Human Well-Being: A Glimpse into the Future with Dr. Álvaro Pascual-Leone
• Digital neurotherapy: bringing neurotechnologies to the patient’s home with Dr. Javier Mínguez
• Rehabilitation Neurotechnology: From the Laboratory to Everyday Life with Dr. Ander Ramos-Murguialday
• Antibiotics of the future: César de la Fuente’s innovative approach
• Future and Life: Keys to Synthetic Biology with Marc Güell