Project AIRMAIL: Using AI for LNP Formulation of RNA & DNA Actives

Edition 2 / June 2023

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Author
Adriano Indolese,
Head of Development & Innovation
CordenPharma International

Project AIRMAIL – Artificial Intelligence in Drug Development: Machine Learning Algorithm for the LNP Formulation of RNA & DNA Actives

[Photo by Wacker] The “Project AIRMAIL” team kick-off meeting at the Wacker facility in Munich, DE on 29 March, 2023. From left to right: Susanne Petzel (LMU), Tim Kramer (CP), Olivia Merkel, (LMU), Mareike Hüttenschmidt (CP), Ahme Igra (HUB), Fabian Hogenkamp (CP), Andreas Heindl (CP), Valentin Fell (LMU), Christoph Arentz (HUB), Adriano Indolese (CP), Hagen Richter (Wacker)

After the overwhelming success of RNA-based COVID-19 vaccines, great potential is envisioned for other RNA-containing medical drugs. In addition to vaccines, treatments against cancer or hereditary diseases are among the targets of novel RNA and DNA-based therapeutics. In general, Lipid NanoParticles (LNPs) are used to encapsulate RNA and DNA to ensure its integrity, allow its transportation into cells, and release the pharmaceutically-active RNA and DNA at the desired target.

On 30 March 2023, CordenPharma, WACKER, the Ludwigs-Maximilians-University Munich (LMU) and the Humboldt-University Berlin (HUB) put out a press release announcing their joint collaboration to accelerate research on novel LNP technology through the so-called “Project AIRMAIL”, which is funded by the German Federal Ministry of Economic Affairs and Climate Action. A major drawback in “traditional” LNP development is that it primarily relies on extensive screening experiments to find not only the suitable lipid structures, but also a balanced mixture of several lipid types for a given application. The Project AIRMAIL team combines several competences to make LNP formulation development faster, more efficient, and less expensive. With the help of machine learning, RNA-LNP formulation experiments will train an algorithm, which finally predicts required lipids to encapsulate an RNA molecule of interest in the best LNP possible, and finally create the most effective RNA pharmaceutical.

Based on our long experience, CordenPharma focuses on the synthesis of novel lipid structures and competence in lipid synthesis and production. With the successful Botanichol^® process in hand, high quality starting materials for novel cholesterol-based lipid derivatives for LNP formulation are readily available. Furthermore, CordenPharma will combine its competencies in lipid and peptide synthesis to design novel hybrid structures that help improve LNP technology even further.

Project AIRMAIL relies on a strong collaboration of all involved partners, where CordenPharma will provide new lipids, while WACKER supplies RNA samples. In the first phase of the project, Professor Arenz (HU Berlin) and Professor Merkel (LMU Munich) will use the substances in formulation and characterization studies to investigate the performance of new LNPs. With the data generated in those experiments, a machine learning algorithm will be set up and trained by the group of Prof. Merkel in Munich. During this phase, the AI will learn from the experimental data and will finally be able to universalize the structure-property relationship of new lipids in LNP formulation. In the end, the algorithm will custom-fit certain lipid structures to an RNA molecule of interest, which will allow the formulation of the most effective LNP possible for the certain RNA sequence. In the last phase, the functionality of the system will be tested in a practical application.

The research will be done at CordenPharma Frankfurt by the newly formed Innovation Chemists team and will run for three years, starting from April 2023. The joint research Project “AIRMAIL” is funded with a total amount of €1.4 million.

[Photo by CordenPharma] CordenPharma´s Project AIRMAIL team in Frankfurt, DE. Left to right: Dr. Fabian Hogenkamp,
Dr. Mareike Hüttenschmidt, Dr. Andreas Heindl, Dr. Tim Kramer