Nanoheme

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. 

Sponsorship

Interested in learning more and supporting this project? Check out Kelserra's sponsorship catalog below!

Nanoheme.pdf

Recruitment

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.