In this new NANEMIAR interview, we spoke with Léa Girondier (CNRS), a researcher in the project, who shares her experience in the development of new therapeutic strategies for congenital anemias. Throughout the conversation, she explains her role in conducting experiments using ex vivo and in vivo models, the technical challenges involved in optimizing protocols within complex biological systems, and the importance of validating results before potential clinical application. She also reflects on the potential of mRNA-based therapies to improve red blood cell production and their impact on patients with beta-thalassemia and other hereditary hematological diseases.

What is your role in the project?
"I conduct experiments in the laboratory (ex vivo) and in living models (in vivo) to test a new approach aimed at improving red blood cell production. In other words, as an engineer, I optimize protocols to evaluate this therapeutic approach in models that best replicate physiological and pathological conditions."

What motivates you?
"Understanding biology, sculpting protocols regarding the previous results and seeing a concept move from theory to a real biological effect is very motivating. It’s the point where research starts to feel like it could truly make a difference and impact patients’ lives."

Why are in vivo approaches important?
"What works in isolated cells doesn't always work in a whole organism. In vivo testing allows us to observe the overall effect of the treatment, particularly on red blood cell production, as well as on safety and side effects. That is an essential step before considering application in humans."

What technical challenges do you face?
"The development and optimization of protocols is a central challenge of the project. It is not simply a matter of applying a standard method but of continuously adapting it to complex and variable biological systems. Each sample can respond differently, requiring fine-tuning of experimental conditions, sometimes in real time. Example, The challenge is twofold: to obtain reliable and reproductible results while staying as close as possible to physiological and pathological conditions. As a in vivo perspective only, the challenge focuses on variables, more un certainty and there are also strict ethical requirements, so everything has to be carefully designed and justified."

How do you evaluate your results?
"As they mature, red blood cells acquire specific characteristics that can be identified. I analyze these features in both diseased and healthy models, treated or not with mRNA treatment. As well, I search for any toxicity-related and look for reproducibility of the results."

What is the overall challenge of the project?
"The main challenge is bridging the gap between experimental results and clinical application. Our part in our team plays a key validation role. If we see positive results in vivo, it strongly supports the relevance of our approach and brings the project one step closer to clinical application. We must ensure that the effects observed in the lab can be translated into tangible benefits for patients."

What impact could this project have on patients with beta-thalassemia?
"The goal is to promote the production of functional red blood cells. If the in vivo results are successful, it suggest we are getting closer to a treatment for beta-thalassemia patients that will reduce the need for transfusions and improve quality of life. NANEMIAR also provides proof of concept for other congenital anemias. As such, the project could extend beyond beta-thalassemia to other conditions, such as Fanconi anemia."

If you had to summarize your role in one sentence?
"I turn biological hypotheses into concrete experimental results to bring research closer to clinical application."