Moderna Announces Recent Advances in mRNA Technology Platform to Improve Delivery and Stability

Today, Moderna held its fifth Science and Technology Day eve.

Recent Advances in Inhaled mRNA Delivery Technology

Moderna's executives pointed out in the report that as of the first quarter of 2022, Moderna's research and development pipeline contains 46 research and development projects, covering a variety of different treatment modaliti.

Most mRNA delivery methods require mRNA to be encapsulated in lipid nanoparticles (LNPs), which are composed of a variety of lipids, and their formulations need to be optimized for the best delive.

▲LNP is the main way to deliver mRNA therapy (Image source: Moderna’s official website)

For lung diseases, inhaled mRNA therapy can maximize the concentration of drugs in the lungs compared with other delivery methods, and can be used to treat a variety of diseases, such as cystic fibrosis (CF), tuberculosis, new coronary pneumonia, chronic Obstruction of the lungs,e.

The Moderna researchers initially found that mRNA delivered using previous formulations of LNPs did not efficiently drive reporter protein expression in lung epithelial cel.

▲Technology for tracking inhaled mRNA delivery and protein expression (Image source: Moderna’s official website)

Studies using an in vitro lung tissue model found that although mRNA-carrying LNPs were taken up by 60% of lung epithelial cells, only 1% of cells were able to express the protein encoded by the mR.

Based on this understanding of the details of the mRNA delivery process, the researchers focused on improving the LNP formulation while maintaining the efficiency of LNP uptake by cells, optimizing protein expression, and ultimately significantly increasing the expression levels of mRNA delivered by the inhaled LNP formulation in lung epithelial cel.

▲Optimizing LNP absorption and protein expression for LNP formulations for pulmonary delivery (Image source: Moderna’s official website)

In a non-human primate model, aerosol-delivered inhaled mRNA drugs are able to drive widespread protein expression in the airway epitheli.

Image source: Morderna official website

Moderna has partnered with Vertex to develop an inhaled mRNA therapy expressing CFTR for the treatment of cystic fibros.

Recent Advances in Improving mRNA Drug Stability

mRNAs are inherently unstable, so if they are to be developed into therapeutics, improving the stability of mRNAs has very real implications in extending drug storage and shelf li.

In their study, researchers at Moderna found that ionizable tertiary amines in LNP formulations can chemically react with mRNA to form adduc.

Image source: Moderna's official website

The company's research points to the need to use different means to reduce adduct formation during the production of mRNA-carrying LNPs, which could lead to multiple benefits, including improved product shelf life and the ability to store products at higher temperatures, And maintain product activity and consistency between manufacturing batch.

In Moderna's Science and Technology Day report, the company also presented in vivo biodistribution data for the intramuscular mRNA vaccine, as well as the company's model to guide vaccine dose selecti.

Attached PPT

References:

[1] MODERNA ANNOUNCES ADVANCEMENTS IN MRNA PLATFORM SCIENCE FOR APPLICATION ACROSS MULTIPLE DISEASES AT SCIENCE AND TECHNOLOGY D.

[2] Moderna Science & Technology Day 202 Retrieved May 17, 2022, from https://s2q4c.