NIH Reporter #1P01HL187309-01

Optimized Nucleic Acid and Cell Specific Delivery Core

This award funds Core B to design and optimize mRNA sequences and lipid nanoparticle formulations for targeting hematopoietic stem cells across multiple species, supporting a multi-project NIH effort to develop clinically relevant delivery systems for hematological disorders.

Description

Core B will provide key support to all three projects described in the Targeting Hematopoietic Stem Cells by Lipid Nanoparticles to Treat Hematological Disorders P01 proposal. Core B will design, produce, and optimize messenger RNA (mRNA) sequences used in each of the three projects. Core B will formulate optimized mRNA sequences into lipid nanoparticles (LNP) and perform surface modification as needed. Core B will design, synthesize, and screen novel ionizable lipids (iLs), including ILs optimized for improved ionization and cleavage under hypoxic conditions. Core B will optimize and produce formulations for HSC targeting across species and in different disease models. Core B will perform HPLC-CAD analysis, quality control, and release testing on all formulations. Core B will develop and validate methods and protocols to study the biodistribution and potency of multiple formulations in one animal using oligonucleotide and peptide barcoding techniques. Core B will perform process development to produce mRNA-LNP for NHP and sheep studies. The goal of Core B is to support the work of all three projects and help develop a novel, clinically relevant, and highly effective lipid nanoparticle formulation for HSC targeting across species.

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