By Dr Sergio López-Manzaneda


Sergio López-Manzaneda, researcher in the labMy name is Sergio López-Manzaneda, PhD, and I am a researcher at the Department of Epithelial Biomedicine within the Biomedical Innovation Unit at CIEMAT/ Fundación Jiménez Díaz, based in Madrid, Spain.


Which aspect of EB are you most interested in?

My research is focused on recessive dystrophic epidermolysis bullosa (RDEB). My connection to EB stems from my background in gene therapy and gene editing for rare conditions. EB is caused by a change to a single letter in the DNA code (point mutation), rather than larger pieces of DNA being changed, missing or repeated. Genetic conditions caused in this way are ideal candidates for new treatments using gene editing technology, such as CRISPR/Cas9. However, different EB families can have different single letter changes within the same gene and one gene editing treatment could be suitable only for one or two families. In this project, our focus is on generating 'genetic patches', for small regions of the large RDEB gene where several different genetic changes that cause RDEB occur. We aim to combine CRISPR/Cas9 directed gene cutting technology and our ‘genetic patches’ to repair the DNA of skin cells from groups of patients whose genetic changes are not identical but occur in the same part of the gene. Strategies like this, that are applicable to multiple genetic changes simultaneously, increase the number of people potentially benefiting from each of these individual gene therapies.


What difference will your work make to people living with EB?

My work uses CRISPR/Cas9, a new tool that allows us to cut a person’s DNA wherever we want. We have designed small molecules to guide this cut close to the genetic changes that cause RDEB. The goal is to force skin cells in the laboratory to repair these cuts, using our DNA “patches” as templates, so the correct gene sequence is restored. A skin graft would then be grown from the repaired cells of the patient. As this graft would be made from a person’s own cells, there should be no attack from their immune system on the new, healthy, skin as would be likely if skin was transplanted from another person.

Any advancements in the field of gene editing concerning RDEB contribute significantly to the overarching objective of advancing new types of therapies. Ultimately, these advancements aim to one day translate into real treatments that will improve quality of life for people living with EB. Each new strategy not only broadens our options for EB gene therapy, but also enhances our knowledge and understanding of EB. These collective efforts strengthen the EB research community, equipping us with greater wisdom and more options to confront the complexities posed by EB. Every step forward brings us closer to offering real solutions and improving the lives of those affected.


Who/what inspired you to work on EB?

Knowing the type of symptoms and what they mean for patients is enough inspiration to work on new therapies. Moreover, understanding that even small advances in patient wellbeing could significantly transform the lives of people living with EB and their families fuels our unwavering commitment to this research. Every step taken towards improving gene editing technology, irrespective of its scale, has the potential to profoundly alter the lives of people living with EB. This recognition instils in us a resolute dedication to furthering gene editing technologies, aiming to revolutionize treatments and elevate the overall quality of life for those affected.


What does the funding from DEBRA mean to you?

Like many other advanced technologies, CRISPR/Cas9 gene editing is financially demanding. Additionally, rare diseases often don't receive significant attention from major pharmaceutical companies. This is where the assistance from charities like DEBRA UK becomes pivotal in sustaining and propelling our research endeavours. Their support is instrumental in making our project viable and driving its success. We are immensely grateful for the invaluable support received, as it significantly contributes to the feasibility and progress of this project.


What does a day in your life as an EB researcher look like?

A typical day in EB research has three distinct parts. Firstly, as a team coordinator, the focus is on managing the team's needs, addressing doubts with reassurance, ensuring research plans are being carried out effectively, and preparing for next steps. The second aspect resembles routine work found in many professions, involving the repetition of specific techniques or experiments to gather the results that contribute to our research. Finally, the most imaginative part involves creating fresh strategies and ideas to steer the research in new directions, using the newly acquired results.


Who’s on your team and what do they do to support your EB research?

Research team at CIEMAT, Spain

Our team consists of a few key members, each bringing unique expertise and contributions. Fernando Larcher, our team leader, has extensive experience in the field of EB and other genetic skin conditions (genodermatoses). He serves as the guiding force, offering invaluable insights and direction. Blanca Duarte, our lab technician, knows everything there is to know about running our equipment and carrying out daily experiments. She also makes sure that our results are reliable from one day to the next. Lastly, we have Alex Bassons, our PhD student, whose enthusiasm and fresh perspectives consistently enrich our research plans, bringing new ideas, hope and positivity.


How do you relax when you’re not working on EB?

I enjoy watching films, hanging out with friends, playing video games, dancing, and more. Essentially, anything that allows me to savour moments with my family and friends brings me joy. Whether it's exploring new movies, engaging in social activities, or simply spending quality time together, these experiences are what I cherish the most.


What these words mean:

DNA = a molecule consisting of two lengths of ‘bases’, represented by the letters A, C, G and T, twisted around each other in a double helix.

Gene = a sequence of DNA ‘letters’ that ‘spell out’ instructions to make a protein

Gene therapy = adding a working gene to cells where a broken gene is causing a genetic condition

Gene editing = specific methods to repair the DNA sequence of a gene within a genome

Genodermatoses = inherited skin conditions

Point mutation = a single ‘letter’ change in a gene


Full glossary of scientific terms