Lipid nanoparticle delivery of mRNA gene therapy for hemophilia A

The Problem

Hemophilia is a rare genetic condition affecting more than 250,000 people worldwide, according to a 2021 report from the World Federation of Hemophilia [1]. People with the disease lack the ability to produce a blood clotting factor, which is factor VIII for hemophilia A [2]. The current standard of care is factor replacement therapy which requires multiple intravenous injections per week, often starting a young age. This represents a huge burden on patients’ quality of life and creates treatment compliance issues [2]. Gene therapies using single stranded DNA and adeno associated viruses (AAVs) as the delivery vehicle have emerged as a way to stimulate endogenous production of the missing clotting factor [2], [3] Such therapies drastically decrease the treatment frequency [3], [4]. However, durability of treatment remains an issue, especially in hemophilia A due to difficulties in effectively packaging the larger factor VIII coding sequence into AAVs. Manufacturing AAV-based therapies is also cumbersome and difficult to achieve on a large scale while maintaining appropriate quality [3]. Finally, there is a risk of oncogenic mutagenesis associated with viral integration [5], [6].

The Solution

Nanoheme proposes to design optimized lipid nanoparticles (LNPs) for the delivery of a mRNA gene therapy for hemophilia A. Significant advancements were made in mRNA vaccines delivered via LNPs around the year 2020 as part of the global effort to develop a vaccine for COVID-19. The same technology shows promise to treat many cancers and rare diseases [7], such as hemophilia [5], [6]. There is no risk of oncogenic mutagenesis when using mRNA-loaded LNPs for hemophilia, and no promoter is needed, which decreases the delivery vehicle volume required [5], [6]. The aim of this project is to synthesize and characterize LNPs with adequate packaging capacity for a codon-optimized mRNA sequence corresponding to factor VIII, and that bind specifically to liver sinusoidal endothelial cells (LSECs), where factor VIII is produced naturally in non-carriers of the disease. 


Recruitment 2023 is closed for research members.

Team Leads

Nathan Ruesch

Alongside Elisabeth, Nathan is a Co-team lead for LNP. He is a U1 Neuroscience student who is interested in biotechnology, immunology, oncology, and genetics. 

He enjoys playing chess, playing piano, watching Formula 1, and listening to music.

Elisabeth Lawton

Elisabeth is a Co-team lead for Biodesign’s new Lipid Nanoparticle project. She is a U2 Bioengineering student who is interested in real-world applications of bioengineering to improve clinical standards of care. 

Elisabeth also loves painting and climbing.