A platform technology to rapidly identify novel lipid nanoparticle (LNP) formulations to carry mRNA-based therapeutics to target organs/cells in vivo.

Messenger RNA (mRNA) has emerged as a promising new class of nucleic acid therapy, with the potential to induce protein production to treat and prevent a range of diseases. While significant progress has been made in the design of in vitro-transcribed mRNA, the widespread use of mRNA as a therapeutic requires safe and effective delivery of the mRNA to tissues in vivo.

Ionizable lipid nanoparticles (LNPs) are an emerging method to deliver mRNA to cells in vivo. However, targeting LNPs to deliver their mRNA cargo to a specific tissue of interest following intravenous injection has hampered their utility.

This is a platform technology to screen for novel LNP formulations that optimize mRNA delivery to a desired cell type or organ in vivo.

The technology consists of a library of engineered LNPs that encapsulate functional, custom-designed barcoded mRNA (b-mRNA). These b-mRNA are similar in structure and function to regular mRNA and contain barcodes that enable their delivery to be quantified via deep sequencing.

Using a mini-library of b-mRNA LNPs, a pool of different b-mRNA LNP formulations can be simultaneously administered intravenously into mice as a single pool. The relative delivery efficacy of different b-mRNA LNPs to any target organ can then be determined via deep sequencing to determine the relative abundance of all b-mRNA LNPs in the organ of interest.

• Accelerates the in vivo screening and design of LNPs for mRNA therapeutic applications such as CRISPR-Cas9 gene editing, mRNA vaccination, and other mRNA-based regenerative medicine and protein replacement therapies.
• This platform can be used to identify LNP formulations that target antigen presenting cells for mRNA-based vaccine development.