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The Radboud University iGEM team is dedicated to addressing the daily challenges faced by patients with hemophilia A. This condition is caused by a genetic mutation in the FVIII gene on the X-chromosome, which prevents liver sinusoidal endothelial cells (LSECs) from producing coagulation factor VIII, a crucial protein in the blood clotting process. Our project aims to develop a more effective and comfortable treatment for this genetic disorder compared to current methods.

Hemophilia A

We propose the creation of a niosome vesicle containing mRNAs that encode the coagulation factor VIII protein. These vesicles will be administered into the bloodstream, travel to the liver, and target LSECs with the help of surface proteins. Once inside the cells, the vesicles will release the mRNAs, leading to the production of coagulation factor VIII. This approach enables patients to produce their own coagulation factor VIII, eliminating the need for frequent injections of plasma-derived or recombinant proteins. A visual representation of the vesicle structure is provided below.

Vesicle structure

Our innovative treatment aims to address significant issues with current hemophilia therapies. Presently, patients experience large fluctuations in blood coagulation factor VIII levels after injections, leading to brief stable periods followed by rapid declines. This necessitates frequent injections and risks sudden drops in coagulation factor VIII protein levels, which can trigger hemophilia symptoms. Our mRNA delivery system is expected to provide more stable and prolonged protein levels, reducing the frequency of treatments and associated anxieties.

Graph that demonstrates rapid declines

Additionally, our vesicle-based system offers an alternative to intravenous administration. Recognizing the discomfort of this method, we propose a nasal spray delivery system using hydrogel and vesicles, which allows mRNA absorption through the nasal epithelium. This method promises greater comfort for patients.

Nasal spray

Another critical advantage of our approach is the elimination of the risk of viral infections, such as HIV and HCV, which can occur with human plasma-derived treatments. While rare, such infections are possible. By avoiding human-derived components, our treatment ensures safety from these risks.

Human holding heart, symbolically representing safety

Hemophilia is a widespread condition affecting approximately 1,125,000 people worldwide and we, as a group of young scientists, are committed to enhancing the quality of life for these patients. In severe cases, hemophilia can lead to fatal blood loss, but even minor inconveniences, like restricted physical activities, significantly impact patients' lives. Our project aspires to contribute to a better quality of life for those affected by hemophilia, addressing both major and minor challenges of the current treatment landscape.

Reference Articles:

  1. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909888/
  2. Systemic delivery of factor IX messenger RNA for protein replacement therapy:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347596/
  3. Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208951/
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