2024 - Nanbiosis

Nanotechnology to slow down the growth of glioblastomas

Directors of Unit 20 and Unit 3, Ibane Abasolo and Miriam Royo, show us the ReachGlio project, which uses nanomedicines to slow glioblastoma growth by targeting tumors in the brain, improving drug delivery through nanoparticles.

Barcelona, october 2024. Each year, on October 9th, Nanotechnology Day is celebrated, a discipline dedicated to understanding and utilizing matter at a nanometric scale for purposes such as industrial or medical applications. Nanotechnology plays a fundamental role in many research lines developed at the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and the Vall d’Hebron Research Institute (VHIR).

“Our goal is to propose one or more clinical trials in patients with glioblastoma using nanomedicines that can efficiently reach the brain and have antitumor activity.”
— Dr. Ibane Abasolo

One of the standout projects in this area is the ReachGlio project, which focuses on improving drug delivery designed to slow the growth of glioblastomas using multifunctional nanomedicines. “Our goal is to propose one or more clinical trials in patients with glioblastoma using nanomedicines that can efficiently reach the brain and have antitumor activity,” explains Ibane Abasolo, the project’s principal investigator.

ReachGlio is part of the TRANSCAN 3 program, involving seven European entities, including two Spanish institutions: the Instituto de Salud Carlos III (ISCIII) and the Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN). The Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and the Vall d’Hebron Research Institute (VHIR) participate through the CIBER-BBN groups led by researchers Miriam Royo and Ibane Abasolo.

Nanomedicines with antitumor activity

Glioblastomas are among the most aggressive tumors due to their location within the brain and their ability to invade surrounding tissue. Additionally, they are highly heterogeneous tumors. All of this explains why the prognosis for patients with this type of tumor remains very poor, with no curative therapy options available.

“One of the main challenges for drugs designed to slow the growth of glioblastomas is how difficult it is for them to effectively reach the brain and distribute homogeneously within such a diverse tumor,” explains Miriam Royo, researcher of the project.

“One of the main challenges for drugs designed to slow the growth of glioblastomas is how difficult it is for them to effectively reach the brain and distribute homogeneously within such a diverse tumor.”
— Dr. Miriam Royo

To overcome this obstacle, the current project proposes the use of nanoparticles that incorporate existing drugs, which, although they have already proven capable of slowing tumor cells, have difficulty accessing the brain. These nanoparticles, specifically polymeric micelles, have small peptide sequences on their surface that act as targeting molecules. These peptides help the nanoparticles cross the blood-brain barrier, between the blood vessels and the brain, and once inside the brain, they guide them towards the tumor cells.

During the project, a drug (NGR-TNF) will also be tested, which makes the blood-brain barrier more permeable, in combination with antitumor treatments or the nanomedicines being developed. “This specific part is planned to be tested at the veterinary level in dogs that already suffer from spontaneous brain tumors, so we hope the project’s results can quickly reach glioblastoma patients,” adds Ibane Abasolo.

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What is NANBIOSIS?

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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Harnessing Nanotechnology in protein research: Insights from Dr. Neus Ferrer on new ways of fighting antimicrobial resistance

Dr. Neus Ferrer explores nanotechnology in protein research to combat antimicrobial resistance, focusing on innovative solutions using lysins and other recombinant proteins.

Barcelona, October 2024. In celebration of Nanotechnology Day, we take a closer look at the cutting-edge work of Dr. Neus Ferrer, director of the Unit 1, Protein Production Platform (PPP), at NANBIOSIS. Specializing in recombinant protein synthesis, Dr. Ferrer’s research tackles critical challenges in healthcare, particularly antimicrobial resistance, often referred to as the “new pandemic”. Through advanced nanotechnology approaches, her team in develops innovative solutions that could revolutionize treatment options in biomedicine and beyond.

The interview begins…

Interviewer: Welcome to these interview series, Neus. Let’s get started. First of, could you share with us a bit about your research area and the projects you’re currently working on?

Neus Ferrer: Throughout my career, I’ve mainly focused my projects on the production of recombinant proteins. In this field, I’ve worked on many areas related to biomedicine, primarily cancer and antibiotic resistance. Lately, I’ve been more focused on the latter: exploring new alternatives or synergistic possibilities with the use of antibiotics.

Antibiotic resistance is often referred to as the “new pandemic”, a massive issue. Many of us know people affected by antibiotic resistance: infections that aren’t detected in time or are misdiagnosed, which leads to resistance. this is sometimes the case of nosocomial infections. This requires us to update our tools to fight these resistant infectious agents. Could you tell us more about the strategies you use to tackle this problem?

Neus: Based on our understanding of how organisms interact with these microorganisms to overcome infections and how they communicate to inhibit or proliferate, we extract the factors that help control microorganisms and formulate them to interact at the infection site. All this is done using the same biological language that exists in these relationships. It’s basically combining the natural mechanisms that we and the scientific community have been investigating and discovering.

Could you give us a recent example of a strategy you’ve used in a project or publication you’re working on?

Neus: Yes, for example, we recently worked on producing proteins with notable antimicrobial activity: lysins. These are used by bacteriophages after completing their cycle [within the bacteria] to release themselves into the environment, meaning they can lyse and eliminate bacteria. Using this activity, we can also formulate these proteins to act on microorganisms in a somewhat specific way —not entirely, but it can be modulated.

Interesting. Tell us a bit about yourself on a personal level. What motivated you to pursue a career in science? What sparked that curiosity that all scientists seem to have?

Neus: I suppose it’s the curiosity of wanting to understand why we’re here, what we are, and how life works. How we function on a molecular level, how these interactions happen. I think it’s about finding meaning in what we do here, answering the question of where we’re going and what we’re doing.

That curiosity seems to be a common thread. Many people I’ve interviewed say the same thing. Have you had any “Eureka” moments in your career? Anything that stands out as your biggest contribution to your field, either professionally or personally?

Neus: I don’t think I’ve had any major “Eureka” moments, but rather several moderately intense ones. I remember during my PhD, at the time, recombinant techniques weren’t widely used yet, so I had to purify a protein from its natural origin, which was a very long and tedious process. When I finally managed to purify and identify the protein, that was a real “Eureka” moment for me —more on a personal level than in a professional one.
Later on, I had another moment while looking back at my work and reviewing the progress in recombinant proteins in the biopharmaceutical field. Summarizing and reflecting on the field was another significant “Eureka” for me because it allowed me to consolidate my experience along with that of others and present it in a way that could be useful to others.

It must be gratifying to see how much progress has been made with recombinant techniques, which you witnessed at their inception. Could you explain the recombinant technique to a general audience?

Neus: In biological systems, proteins perform numerous functions, but there are control mechanisms, and they’re only produced when needed. If you identify a protein with a function that’s useful for biomedicine, in natural systems, you typically have very small amounts. This was a drawback because you needed large quantities to get a little of the target protein. With molecular biology techniques, it’s possible to introduce genetic material into a cell artificially, making the cell produce a specific protein. This allows for large-scale production, which was revolutionary.

“With molecular biology techniques, it’s possible to introduce genetic material into a cell artificially, making the cell produce a specific protein. This allows for large-scale production, which was revolutionary.”
— Dr Neus Ferrer

By introducing external genes, you’re essentially turning organisms into protein factories. But earlier, you mentioned lysins, which are designed to kill bacteria. How do you prevent the bacteria from dying as they produce these proteins?

Neus: That’s an interesting question. Initially, we thought there would be difficulties producing these proteins within bacterial cells, as they have the activity of lysing them. However, we selected lysins that could theoretically be produced in our best prokaryotic production system, Escherichia coli. Additionally, we formulated the proteins in a way that they form small protein nanoparticles, reducing the biological activity within the cell.

So, the proteins naturally form these structures, preventing the bacteria from being affected by the lysins. Fascinating. Moving on to a more personal topic: What advice would you give to young people considering a career in science?

Neus: I’d encourage them to be brave, especially women. We need more women in science because society is 50% women, and science should reflect that. They should believe they can achieve the same or more than men, and I pass the torch to both men and women to move forward with their ideas.

What have been the biggest challenges you’ve faced in your scientific career?

Neus: Job stability is the biggest challenge. The field is very competitive, and you have to give your 150-200%. But if you have that curiosity and motivation, you need to keep pushing forward. There are many success stories, like mine, where we’ve stabilized later in my career. So, I encourage everyone with that curiosity to pursue it and keep trying.

What support have you found most helpful in your career?

Neus: Collaboration is key. It’s crucial to share ideas and work as a team. Many opportunities arise from collaborations, whether it’s through partnerships or learning about new opportunities.

That’s far from the fictional image of the lone scientist in a lab. Collaboration is essential. And this is exactly what NANBIOSIS promotes. Can you tell us about the Unit you work in within NANBIOSIS and your role in it?

Neus: I’m in Unit 1, the Protein Production Platform (PPP), where I’m the scientific director. Since 2007, we’ve worked on over 400 projects, interacting with CIBER groups, companies, hospitals, technology centers and universities, including the university we are located at, the Universitat Autònoma de Barcelona.

That’s a beautiful journey from your early thesis days to leading a platform that returns research to society. How does NANBIOSIS contribute to academic research?

Neus: We’ve seen how our support helps researchers grow their projects in a wide variety of areas. We centralize knowledge and offer methodologies that would take years for groups to develop on their own. The projects that we work in are from a high level of complexity. It’s a challenging, but very rewarding role.

What about the private sector? How can NANBIOSIS contribute to the industry?

Neus: We’ve collaborated with the industry at various levels, helping with basic research and diagnostics. It’s different from academic work, but equally gratifying. Though you might not see the results for years, knowing you’ve contributed to a product reaching a patient is very fulfilling.

NANBIOSIS has Cutting-Edge Biomedical Solutions (CEBS) that present synergies between the Units in the network. How do these help solve market problems?

Neus: We offer a platform that can assist clients through the process, from basic research to a pre-clinical stage. Our expertise in recombinant proteins is crucial for this, and we are capable of producing recombinant proteins of any kind. We have the know-how and the capabilities for doing si.

How has NANBIOSIS contributed to your career?

Neus: NANBIOSIS has allowed me to materialize my knowledge into a platform that can pass this on to the future —whether through students or external clients. It’s a way to give back. We see this in a daily basis, because there are always students that come along with us who learn our methodologies. Our external clients also learn from us if they need it, not just providing them with services. For me, NANBIOSIS is all that: the ability, one way or another, to trasnfer the knowledge I acquired during all these years and make it tangible.

Thank you, Neus, for your time and insights.

Neus: Thank you! See you again.

This interview is fully available in Spanish in our Youtube channel (click here).

What is NANBIOSIS?

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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Latest breakthroughs in pulmonary drug delivery and cancer research at NANBIOSIS

On World Pharmacists’ Day, NANBIOSIS Units highlighted for breakthroughs in pulmonary drug delivery and cancer research, advancing treatments for respiratory diseases and brain cancer.

Barcelona and Zaragoza, September 2024. On World Pharmacists Day, we celebrate the vital contributions pharmacists make, not only in patient care but also in groundbreaking research that is shaping the future of healthcare. This year 2024, we want to give this significant date a little twist: by showcasing a few examples of how our Units are contributing to healthcare and new pharmaceutical approaches. Two key NANBIOSIS units —Unit 9 and Unit 25— are at the forefront of said scientific advancements, offering promising solutions for respiratory diseases and cancer treatments.

Innovative pulmonary drug delivery

One of the most appealing means to treat respiratory diseases is the delivery directly into the lungs by the use of aerosols containing the drug. This allows having a highly concentrated drug dose in the affected tissue, without exposing the rest of the body to it. However, when done as a dry aerosol powder, this strategy suffers an important drawback: the difficult dispersion of solid particles whose sizes are in the micron or even nanometric scale, which tend to form clusters and larger structures and thus hindering the delivery. And this is where Unit 9 comes to play.

In collaboration with the University of Zaragoza (UNIZAR), our researchers M. Pilar Lobera, Jesús Santamaría and their coworkers, have made remarkable strides in improving this type of pulmonary drug delivery. They have developed an advanced aerosol generator that addresses key limitations in traditional inhalers, including inconsistent dosing and poor control of particle size.

“All nanoparticles used in the validation of this method of aerosolization were synthesized by Unit 9, using coprecipitation, microfluidics or electro-spraying methods.”
— M. Pilar Lobera

This aerosol generator delivers highly dispersed particles directly to the alveoli, the deepest part of the lungs where drug absorption is most effective. The technology offers several crucial benefits:

Precise particle control for targeted lung delivery, free of aggregates.
Improved bioavailability, ensuring more effective treatment targeting the alveoli and other targeted regions within the lungs.
Reproducible dosing across different patients, regardless of how damaged is their lung function.

These advances have the potential to revolutionize the treatment of respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and lung cancer. Capable of aerosolizing a wide range of particles containing diverse biomolecules, including proteins and peptides, the device also shows promise for inhaled vaccines.

A) SEM images of original dry powder formulation. B) SEM image of captured drug in aerosol phase C) TEM image of captured drug in aerosol phase C) Particle size distribution in the aerosol obtained was analyzed in real time using a Scanning Mobility Particle Spectrometers with Condensation Particle Counter as detector, SMPS+C: Foster NextHaler: GMD = 44 ± 1.7 nm; ~ 2400 #/cm3; Ultibro Breezhaler ®: GMD = 70 ± 5.4 nm; ~ 8700 #/cm3

In testing, the device achieved a fourfold increase in alveolar deposition compared to current inhalers, with 99% of particles sized optimally for deep lung delivery, all the way into the alveoli. This breakthrough marks a significant step forward in making inhaled therapies more effective and accessible for patients.

Advancing cancer research

Meanwhile, at NANBIOSIS Unit 25, located at Universitat Autònoma de Barcelona (UAB), researchers are pushing the boundaries of cancer treatment through cutting-edge imaging technologies. Ana Paula Candiota explains to us how their Bruker 7T MRI/MRS/MRSI preclinical scanner allows scientists to noninvasively monitor cancer progression in live animal models. This is particularly interesting in orthotopic models, where tumors grow in their natural location. This technology is crucial for accurately assessing the efficacy of new cancer drugs over time, offering an advantage over traditional subcutaneous models.

One of the standout projects at Unit 25 involved testing a novel treatment for glioblastoma, one of the most aggressive forms of brain cancer. Researchers used intranasally administered Catechol-Based Pt(IV) Coordination Polymer Nanoparticles encapsulating cisplatin. This innovative approach reduced the drug’s toxicity while maintaining its effectiveness, showing great promise for noninvasive cancer therapies.

“The encapsulation aimed to reduce cisplatin’s toxicity, and the study yielded promising results.”
— Ana Paula Candiota

The work being done at Unit 25 highlights the importance of advanced technology and collaboration in the fight against cancer. By enabling more precise evaluation of drug effectiveness and reducing harmful side effects, these innovations bring us closer to more targeted, patient-friendly treatments.

For more information about this research, see the original article here: https://doi.org/10.3390/nano12071221

**Top**: examples of tumor volume evolution, T2 weighted MRI and Kaplan-Meier Survival curves which can be obtained in facilities of U25. **Bottom**: the 7T preclinical scanner for MRI/MRS/MRSI of small animals, located at SeRMN-UAB and part of U25.

Celebrating Pharmacists’ impact on research and healthcare

The groundbreaking research taking place at NANBIOSIS Units 9 and 25 reminds us of the essential role pharmacists play, not only in providing care but also in driving medical innovation. Whether that means improving drug delivery systems for respiratory diseases or developing noninvasive cancer treatments, their work is shaping a healthier future for all.

What is NANBIOSIS?

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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Ramón Martínez-Máñez

Born in Valencia on April 11, 1963, Martínez Máñez is one of the national and international leaders in the field of chemical research.

Among other lines of research, his group at the IDM Institute of UPV works on the development of nanometric devices with “molecular gates” for the controlled release of drugs. The studied nanoparticles are capable of retaining a load within their pore system and delivering it upon receiving a chemical, physical, or biochemical stimulus. These particles have been used, for example, for the selective release of cytotoxins to eliminate cancer cells and bacteria, as well as for the release of specific drugs in senescent cells, and for the release of substances in food or agricultural applications.

Additionally, Martínez Máñez’s team is working on the development of molecular probes for the detection, through color and fluorescence changes, of biomedical and environmental elements of interest, such as certain biomarkers or cells, drugs, nerve gases, etc.

Among the multiple recognitions he has received prior to this National Research Award, in 2016 he was honored with the Research Excellence Award from the Spanish Royal Society of Chemistry (RSEQ), and in 2018 with the Rey Jaume I Award for New Technologies.

Author of nearly 600 publications, Ramón Martínez Máñez has a prominent presence in the most significant journals in the field of multidisciplinary chemistry.

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Gene Therapy for Cystic Fibrosis: new inspiring scientific collaboration

Researchers are advancing gene therapies for cystic fibrosis using non-viral delivery methods, focusing on patient needs and innovative treatments.

Basque Country, September, 2024 – As the world comes together to mark World Cystic Fibrosis Day, from NANBIOSIS we want to highlight the collaborative efforts between our Unit 10 “Drug Formulation” (U10), the University of the Basque Country, and the Cystic Fibrosis Patient Association of the Basque Country (Arnasa) in the fight against this genetic condition. Together, our institutions are advancing the development of gene therapies aimed at treating this life-threatening hereditary disease.

Gene Therapy: A new frontier in treating Cystic Fibrosis

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene, which affects the respiratory and digestive systems. Traditional treatments focus on managing symptoms, but the emergence of gene therapy offers new hope for a more effective, long-term solution. Gene therapy introduces functional copies of the mutated gene or corrects specific mutations, addressing the disease at its genetic root.

Unit 10, located at the NanoBioCel research group and led by Prof. José Luis Pedraz and Dr. Idoia Gallego Garrido from the University of the Basque Country, is leading the development of non-viral gene-editing systems to deliver therapies for CF. These systems are being tested in both 2D and 3D in vitro models of cystic fibrosis, offering a cutting-edge approach to targeting the disease.

In a recent interview, Lucía Enríquez, one of our researchers at Unit 10, explained, “Cystic fibrosis is a disease that often involves lung pathology, though it is not the only one. We work on developing therapies that are non-invasive, often of genetic origin, applying the most cutting-edge and effective techniques possible.”

Innovative delivery platforms: A key to success

While viral vectors have historically been used for gene therapy delivery, they present certain risks and limitations, including immune responses and insertional mutagenesis. This has spurred interest in the development of non-viral vectors, such as niosomes and lipid nanoparticles, which offer a safer alternative for gene delivery.

NanoBioCel’s research explores the potential of niosome formulations, in which non-ionic surfactants replace phospholipids, and other promising technologies like nanodiamonds, known for their biocompatibility and scalability. These non-viral vectors are poised to offer a more secure, efficient method for delivering gene therapies, marking a significant advancement in the treatment of CF.

One of the most exciting areas of research is the development of a non-invasive, inhalation-based gene delivery system. This method targets the lungs directly, making it a promising solution for CF, which primarily affects the respiratory system. However, this route presents unique challenges, as genetic material must overcome both intracellular and extracellular barriers within the lungs. Our research team is currently working on designing an efficient aerosol-based delivery system to overcome these hurdles.

Researcher developing lung-on-a-chip models that will simulate the conditions of cystic fibrosis for use as non-animal models to study and assess the efficacy of various therapies.

A patient-centered approach: Collaboration with Arnasa

The partnership between NanoBioCel and Arnasa, the Cystic Fibrosis Patient Association of the Basque Country, is central to the success of this project. Arnasa plays a critical role in ensuring that the research is focused on the real-world needs of patients living with CF. By providing insight into the patient experience and highlighting the most pressing challenges, Arnasa helps guide the development of therapies that can significantly improve the quality of life for CF patients.

Arnasa’s commitment to advocacy and patient support has been instrumental in raising awareness about cystic fibrosis and the importance of investing in innovative research, especially during occasions like World Cystic Fibrosis Day.

Looking to the future

Unit 10 and its collaborators remain dedicated to advancing gene therapies and non-invasive treatments for cystic fibrosis. Through the integration of cutting-edge technology and patient-focused research, they aim to not only improve existing treatments but also create new therapeutic avenues that offer greater hope to those affected by this debilitating condition.

On World Cystic Fibrosis Day, we are reminded of the importance of continued research, collaboration, and awareness to drive progress and deliver better outcomes for patients worldwide.

What is NANBIOSIS?

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

• Read More

New gene therapy for Cystic Fibrosis: an interview with Lucía Enríquez

Vasque Country, September, 2024 – In this interview, Lucía Enríquez, a PhD researcher at NANBIOSIS Unit 10, discusses her work on gene therapies for cystic fibrosis, a genetic disease that mainly affects the lungs. Her research focuses on using non-viral vectors to deliver gene-editing tools, like Prime Editing, a variation of CRISPR-Cas9, to correct mutations at the genetic level. Lucía explains the advantages of non-viral vectors, such as avoiding immune responses and offering safer, non-invasive treatment options. She also highlights the importance of interdisciplinary collaboration, particularly in her work at NANBIOSIS, where advanced drug formulation and pulmonary delivery systems are developed. Lucía reflects on the challenges of pursuing a scientific career in Spain, emphasizing the need for better working conditions and societal support for researchers.

Interviewer: Hi Lucía, tell us a bit about your research area. What projects are you currently working on?

Lucía: I’m currently working on my doctoral thesis in the laboratory of José Luis Pedraz, who is the director of Unit 10 of NANBIOSIS. My thesis focuses on the development of gene therapies encapsulated in non-viral vectors, mainly applied to the treatment of cystic fibrosis, a genetic disease with which our group has been collaborating for a long time. We work extensively on non-viral vectors, almost always applied to gene therapy, as well as other projects related to chemical molecules or other types of therapies.

Something very well-established in our group is that all of these treatments or developments must always be as patient-friendly as possible, meaning minimally invasive. In fact, one of the services we offer at NANBIOSIS is the development and characterization of pulmonary formulations. This is largely due to our experience with cystic fibrosis, as it’s a disease that often involves lung pathology, though it is not the only one.

In summary, we work on developing therapies that are non-invasive, often of genetic origin, applying the most cutting-edge and effective techniques possible.

Interviewer: Non-viral vectors, as I understand, differ from virus-based vectors in that they do not use the mechanisms of viruses. Additionally, they can act at various levels and don’t necessarily alter DNA. Can you tell us a bit more about these mechanisms and how they alter genes or their expression?

Lucía: There are many forms of gene therapy, as you mentioned. Among other types, some modify the genome sequence itself, while others alter the expression of that genome without modifying its sequence.

One of the most important aspects that many research groups focus on is the delivery of these gene therapy tools into the cell. The biggest challenge is ensuring that once inside a complex living organism, like a human, these tools reach the site where we need them to take effect. Historically, the most effective way to deliver these genetic tools was through viral vectors. These are modified forms of viruses that don’t cause the pathology typical of the virus but use the virus’s ability to infect a cell to deliver these genetic tools.

Non-viral vectors aim to achieve that delivery effectively and target the site where they need to act without using a viral vector. This avoids the negative aspects of viral vectors, such as immune responses, gene insertion in some cases, etc. However, non-viral vectors were very inefficient until the development of lipid nanoparticles, which is what the COVID vaccines are made of, where it became clear that this was a very clinically viable option.

Cystic Fibrosis Symptoms. Source: Wikimedia Commons

Interviewer: No doubt that was a global boost, which had been in development for years, and had even been considered for cancer therapies, although outside clinical application. In your case, you say it’s for cystic fibrosis, which is a genetic disease as you mentioned. Do you work at the level of gene expression, at the gene level… what level do you edit at, and what tools do you use?

Lucía: Cystic fibrosis is a genetic disease, as I said, which can be caused by many different mutations. There’s one that is highly prevalent, accounting for over 40% of cases, which is a small deletion of three base pairs that causes issues with a chloride-transporting protein. This affects many organs in the body, but it’s especially important in the lungs because patients with cystic fibrosis accumulate a lot of mucus in their lungs and have serious breathing problems, as well as frequent respiratory infections, etc.

One approach to treating cystic fibrosis at the gene therapy level, which is being led by a colleague of mine who is also working on their thesis, involves delivering a healthy copy of the mutated gene in the form of a plasmid. This means it will promote the functional expression of the gene in a non-pathological way, but it won’t insert into the genome, and the expression won’t be permanent, so the treatment would need to be reapplied.

In my thesis project, we are developing genetic tools based on Prime Editing, which is a variation of the CRISPR-Cas system that corrects the mutation. These tools target the site where the three-base-pair deletion is located and correct it. Here, there is indeed an alteration of the patient’s genome sequence, with the goal of restoring a “wild-type” genotype, or a healthy sequence. This change in the sequence would be permanent in that cell and in all its daughter cells.

Interviewer: Right, when the cell divides, it preserves that gene through subsequent generations. Also, CRISPR has so many applications and is a hot topic. Can you briefly explain what the CRISPR-Cas technology consists of? How do you manage to edit such a specific gene so precisely?

Lucía: The CRISPR-Cas9 technology was discovered because it was originally a way bacteria could defend themselves from viruses. Essentially, it consists of two components: a protein called Cas9, which is a nuclease that cuts the double strand of the genome, and an RNA sequence that we call guide RNA.

The guide RNA scans the entire genome of the cell, and when it reaches a site where the base pairs match perfectly, the Cas9 protein binds to it, recognizes it, and cuts the double strand of DNA. This triggers many DNA repair mechanisms in the cell. If you only introduce the Cas9 protein and the guide RNA, what you usually create is a knock-out (a silenced gene). This happens because the cell tries to repair the sequence at all costs, but it often makes mistakes, like skipping base pairs or adding extra base pairs, in a desperate attempt to avoid cell death.

If, at the time you make the double-strand cut, you also introduce a DNA sequence that matches the genome sequence, there’s a chance the cell will incorporate that sequence as it attempts to repair the break. If you’re introducing a healthy sequence, you’re effectively curing the cell of the genetic disease it had.

What we do isn’t exactly CRISPR-Cas9. We use Prime Editing, which is a variation of this system where the protein doesn’t cut both strands of the DNA, only one of them. This allows you to introduce small insertions, deletions, or base pair changes. In our case, it’s useful because, as I mentioned, one of the most prevalent mutations in cystic fibrosis is a deletion of three base pairs. So, it’s simpler and more efficient in terms of genetic correction to insert those three base pairs using Prime Editing, which is still a variation of CRISPR, rather than introducing an entire genomic sequence to try to repair the gene.

Interviewer: It really is amazing. And this is a system that can be universalized for many different applications, not just for cystic fibrosis. There are so many different genetic diseases, and here you have a tool that you can simply adapt, I imagine, by changing the guide RNA and the sequence you want to introduce. This way, it could be applied to a completely different disease, right?

Lucía: Exactly. In fact, since it was discovered, this tool has been used by many research groups around the world for all kinds of genetic diseases.

Interviewer: Great. Let’s talk a bit about you and your scientific career. On a personal level, what motivated you to choose a career in science? You’re doing a PhD now—what made you think, “This is for me”?

Lucía: It was mainly curiosity. I’ve always considered myself a very curious person, constantly seeking to understand the reasons behind things. In the end, research is about pushing the boundaries of knowledge to go a bit further and see beyond what’s known. That fascinates me on every level, but it also fulfills me personally, because of the kind of person I am—someone who needs to know things, search for answers, solve problems. I think that’s something really cool.

Interviewer: Yes, and it’s something quite common in the scientific world. Many people get into it driven by that initial curiosity, asking, “Why is this like that? Why does it work this way?” Your scientific career has started recently—have you had any “Eureka” moments? Moments where you felt proud of something working out, or something you consider an achievement, either personally or professionally?

Lucía: Well, honestly, I think “Eureka” moments don’t happen that often. If you do have one of those moments, maybe you’ll win a Nobel Prize afterward (laughs). But I think it’s more about the day-to-day—the small achievements, the little things. It also depends a lot on what kind of research you do. If you’re in more basic research, where you’re trying to understand how things work or molecular processes, I think it’s easier to get one of those “Eureka” moments—like discovering the function of a specific protein or the implications of a certain process, etc.

For us, since we do more process development and optimization, unfortunately, 80, maybe even 90% of the results are negative (laughs). I think it’s more about the small wins, taking one step at a time, building little by little, rather than having a big “Eureka” moment.

Interviewer: And constantly hitting a wall, saying “It’s not working, it’s not working…” and then one day suddenly saying, “I did it, I know what went wrong!” Even in that 10-20% of success, it’s very satisfying, right?

Lucía: When it works, it’s very satisfying (laughs).

Interviewer: What advice would you give to young people considering a career like yours in science?

Lucía: When people ask me, I always tell them to explore a lot and talk to people. There’s no wrong path—you can go into research or not. There are many ways to stay connected to science without working in a lab. I think everyone has to find their own path. It’s a beautiful path—I enjoy it, and as I said before, being constantly at the edge of knowledge is very satisfying. But it also demands a level of dedication and sacrifice that not everyone may want in their life. And that’s fine too—it doesn’t make you any less valid if you don’t want this type of life. Plus, that doesn’t mean you can’t stay connected to science. So, talk to people, explore options—there are plenty out there. And that’s it (laughs).

Interviewer: And what do you think have been your biggest challenges in the field of scientific research?

Lucía: I think there have been too many. Everything is a challenge, and if it weren’t, we’d be doing something else, I think. I don’t know, I think when you’re dedicating yourself to learning, literally. There’s a point in the learning phase where you have to understand what’s happening. And that’s always a challenge when there’s no information in that field because, literally, you’re creating it yourself. It’s complex.

Interviewer: And it’s scary—you’re looking into the unknown, it’s the uncertainty, right? You have to enjoy that. How do you think we can encourage scientific vocations among young people?

Lucía: I think promoting a scientific career or this type of life comes down to making it accessible and providing good working conditions. While things have improved, they still aren’t good. Many people are still doing their PhD without getting paid because they don’t have access to a scholarship or funding source. That’s unacceptable. It’s very hard to achieve stability, a long-term career outlook, or a professional life that’s compatible with a personal life. I think that’s challenging, and I believe it’s the responsibility of authorities to promote it.

I also think there’s a societal issue. In Spain, society doesn’t see research as something necessary or even as a real job. I still get asked by people on the street or friends of my parents, “When are you going to stop doing that little course you’re taking?” And I’m like, “Wait, I’m not taking a course!” (laughs). I work in research—this is my job. It hasn’t really sunk in socially. So, if we don’t value it socially, it won’t be valued politically either, and then there won’t be funding. Sure, there are many calls for projects, etc., but the people working in this field need to be able to live, not just survive. They need to live under decent conditions. I think this is what most discourages people from pursuing a scientific career here in Spain, because it’s almost unfeasible.

Interviewer: The issue of job stability is an ongoing battle.

Lucía: To give you an idea, out of my group of friends from university who are doing research, five of us are working on our PhDs. I’m the only one doing it in Spain. Two are in Germany, and two are in the United States. Naturally, they all have a much better quality of life than I do.

Interviewer: It’s interesting because when data comes out about which professions people trust the most, scientists are at the top, even on par with doctors. People trust what scientists say. But as you pointed out, there’s a lack of societal awareness that science requires funding, public investment, and future prospects so that people who want to pursue it can have a stable career and decent working conditions. And many people who go abroad never come back because they’re treated so much better there…

Lucía: I spent 6 months working in a lab in Philadelphia, and the way they treat you—not just in terms of working conditions but also salary and work environment—is important. But what’s really key is the social recognition. Right now, to do a PhD, you need a degree, a master’s, and I’m earning almost the minimum wage, you know? We just want knowledge and qualifications to be valued in a rational way.

Interviewer: It’s not too much to ask…

Lucía: No (laughs). And I think this is important. It frustrates me that this is the reason why many people don’t go into science. There are so many brilliant and passionate people, but they eventually want to buy a house or start a family. And like this, you just can’t. And that’s the reality.

Interviewer: Let’s talk about NANBIOSIS. You work in Unit 10. Can you tell us a bit about what this unit focuses on, your role in the network, and your connection with it?

Lucía: Unit 10 is the Drug Formulation Unit. Essentially, it focuses on the development, characterization, and optimization of delivery systems for active ingredients, which could include chemical molecules, antibodies, proteins, gene therapy, and more. In short, we develop formulations that allow for the efficient delivery of these active ingredients.

This involves developing the optimal non-viral vector for each molecule, the composition of that non-viral vector, its formulation, and characterization. Additionally, we also focus on the characterization of pulmonary formulations, which is another key function of Unit 10. I believe we are a pretty advanced unit because we have pulmonary formulation characterization equipment, which is rare in Spain—there’s maybe only one other place with similar equipment.

Going back to non-invasive therapies, I think the pulmonary route is a very viable option, and it also allows us to characterize formulations intended for ophthalmic or intranasal delivery. Within this context, my role involves conducting experiments and designing them with the groups or entities that contact us to use our services or develop a project.

Interviewer: And connecting to this, how do you think NANBIOSIS can positively contribute to scientific research in the academic world?

Lucía: To be honest, before joining this lab, I didn’t know what NANBIOSIS was. When I discovered it, I thought it was a fantastic opportunity to create networks, collaborate, and connect with people, groups, and entities working on things different from your own. It’s also an ideal way to facilitate knowledge exchange between academia and industry, which I think is very important. Above all, it helps expand your mind and allows you to use your expertise to contribute to the development of others’ knowledge.

Interviewer: I imagine you’re referring to, for example, a company that needs to test a type of formulation or is looking to vectorize a drug or treatment. You provide all that support in terms of know-how, especially considering your lab is cutting-edge, with top-notch equipment and excellent academics. You have true experts in pharmacology, and a company can really benefit from that help.

Lucía: Absolutely. In fact, I think the private industry has the ability to bring the knowledge generated to the market—something that academia doesn’t have the capacity to do, due to the nature of how academia works.

In academia, knowledge is generated, and the industry has the capability to bring it to the market. But there needs to be a common ground between academia and industry for that process to happen. One of the things I like about NANBIOSIS is that it presents itself as a potential point where that connection can happen, and that’s great. As you mentioned, there are a lot of prestigious people in academia. Just to give an example, our principal investigator (PI), José Luis Pedraz, is a member of the Spanish Academy of Pharmacy.

Interviewer: In fact, José Luis Pedraz is “Académico de Número”, a Full Member of the Spanish Academy of Pharmacy—one of the top 50 pharmacists in the country!

Lucía: Absolutely. When it comes to developing formulations or understanding pharmacology processes, honestly, there are few people better in this country than José Luis Pedraz. Having the opportunity, through NANBIOSIS, to have a meeting point with industry to launch that knowledge and enhance that know-how, as you mentioned, is truly a fantastic opportunity.

Professor Jose Luis Pedraz Muñoz, **director of Unit 10**, officially inducted as an “Académico de Número”, the highest position within the Royal National Academy of Pharmacy.

Interviewer: Great. And how has NANBIOSIS contributed to your scientific career? I understand you work with the services NANBIOSIS offers and are developing your research—what has it provided you with professionally?

Lucía: As I mentioned, NANBIOSIS is a meeting point for different groups and entities, and it has given me the opportunity to connect and understand how people working in different research fields think. This is crucial if you’re in science. Progressing in science without interacting with other areas is almost like failing in the attempt, and José Luis understands this very well: you need to collaborate and understand all the fields developing around you.

In fact, it was one of the reasons I chose to do my PhD here—because of the culture of collaboration and working with other groups. We work with a couple of groups that are engineers specializing in developing materials and devices for medical applications. This is something you don’t initially consider, but when you have your formulation with your gene therapy all ready to go, you might then ask, “How do I administer it?” Having the opportunity to talk to people who develop delivery devices or understand that part of the process that you might not cover—because we can’t do everything—is vital for your development as a scientist and for understanding everything happening around you.

Interviewer: In addition, NANBIOSIS has a wide range of Units and a very broad, multidisciplinary service portfolio, which is absolutely essential in research and technology transfer today. In fact, this leads nicely into the next question: At NANBIOSIS, we have the Cutting Edge Biomedical Solutions, which involve combining several services from various Units to address a market problem or an industrial challenge. This aims to provide solutions to the industry on issues that require that know-how and the interconnection and synergy between the Units. You have been involved in several of these Cutting Edge Biomedical Solutions; could you give us a brief overview of them?

Lucía: Yes, currently we have three active ones, if I remember correctly. They all revolve around nanomedicines and non-viral vectors, encapsulating active ingredients, cells, genetic material, proteins, etc.

One is focused on the physicochemical characterization of these nanomedicines themselves. Having them well-characterized and studied allows us to understand exactly what’s happening and makes the scaling process easier.

Another one is about in vitro characterization of these nanomedicines. This means studying how they behave in pathological models or cellular models in two dimensions. This allows you to start fine-tuning the formulations or nanomedicines to ensure they have biological activity.

The third one is about in vivo characterization of these medicines. This helps you understand how these nanomedicines work within a more complex organism compared to a two-dimensional cell culture. Using experimental animals, you can study how they distribute within the organism, how effective they are, etc. This enables a better understanding of how the therapy works and optimizes it in a complex organism before moving on to human clinical trials.

All three together cover the necessary steps before reaching clinical trials.

Interviewer: They are essential in the transfer and translation of new therapies, and require a lot of hands-on work and cutting-edge facilities. One last question: How do you see yourself in 5 or 10 years?

Lucía: To start with, I hope to be a doctor (laughs).

Interviewer: How long have you been working on your thesis?

Lucía: Well, it’s been about two and a half years now, so we’re about halfway through. And then… I don’t know. Science is something that I really like and motivates me a lot, and it’s always been part of my life’s project. I think this happens not only to people in science: if you dedicate yourself to something that motivates you a lot and you’re willing to give it 100% every day, it becomes part of your life’s project, not just your job. But it’s not my only life project (laughs), so… we’ll see. We’ll see what opportunities arise, whether I can continue dedicating myself to science or if it stops being viable. As I mentioned before, it’s not an easy path; I might be able to pursue science… but maybe not in this country. I don’t know, we’ll see.

Interviewer: We’ll see. Thank you very much for these minutes. It’s been a pleasure, Lucía. We’ll stay in touch.

Lucía: Likewise, see you later!

You can watch the full interview here (Spanish):

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What is NANBIOSIS?

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Custom solutions

Cutting-Edge facilities

Standards of quality

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References:

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Cutting-Edge facilities

Standards of quality

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Standards of quality

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Cutting-Edge facilities

Standards of quality

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Cutting-Edge facilities

Standards of quality

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Antonio Villaverde