Nanoparticle Mediated Delivery of Therapeutic mRNA for Protection Against Lung Damage

Technical Report · Fri Oct 01 04:00:00 EDT 2021

DOI:https://doi.org/10.2172/1891377· OSTI ID:1891377

Branda, Steven ^[1]; Mosesso, Richard ^[1]; Sinha, Anupama ^[1]; Thatcher, Christine ^[1]; Collette, Nicole ^[2]; Phillips, Ashlee ^[2]; Tanner, Tanya ^[2]

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1. Sandia National Lab. (SNL-CA), Livermore, CA (United States)
2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

Medical countermeasures (MCMs) based on messenger ribonucleic acid (mRNA) are promising due to their programmability, targeting precision and specificity, predictable physicochemical properties, and amenability to scalable manufacture. However, safe and effective delivery vehicles are needed, especially for targeting the lung. We developed a generalized approach to nanoparticle-mediated mRNA delivery to lung, and used it to evaluate candidate therapies. In initial studies, reporter mRNA was delivered using lipid-coated mesoporous silica nanoparticles (LC-MSNs) and lipid nanoparticles (LNPs), the latter with greater consistency. Then, mRNA encoding known protein therapies were delivered using LNPs. These formulations showed some toxicity in mice with lung damage, but those with IL-1RA, sACE2-Ig, and ANGPT1 mRNA were modestly therapeutic on balance. Our work advances the state of the art for mRNA delivery to lung, and provides a foundation for evaluating and characterizing mRNA-based lung therapies, including three that appear to be exceptionally promising.

• Research Organization: Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
• Sponsoring Organization: USDOE National Nuclear Security Administration (NNSA)
• DOE Contract Number: NA0003525
• OSTI ID: 1891377
• Report Number(s): SAND2022-13801; 710679
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
77 NANOSCIENCE AND NANOTECHNOLOGY