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Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
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Localization of Intramuscular mRNA Delivery Using Deep Eutectic-Lipid Nanocomposites
Alexander Michael Curreri1,2, Michael Dunne1,2, Michael Griffith Bibbey1,2
1John A. Paulson School of Engineering and Applied Sciences, Harvard University, 150 Western Ave, Allston, MA, 02134, USA.
Advanced Healthcare Materials
|May 2, 2024
Summary
This study introduces a novel deep eutectic-lipid nanocomposite for messenger ribonucleic acid (mRNA) delivery. This system enhances local muscle expression and reduces off-target liver expression for improved therapeutic efficacy.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery Systems
Background:
- Messenger ribonucleic acid (mRNA) therapeutics offer potential for various diseases but face delivery challenges.
- Traditional lipid nanoparticles (LNPs) can cause systemic exposure, impacting efficacy and safety.
- Current mitigation strategies often involve complex lipid or LNP redesign.
Purpose of the Study:
- To develop a novel deep eutectic-lipid nanocomposite for tunable mRNA expression.
- To evaluate the efficacy of this system for intramuscular mRNA delivery in vivo.
- To investigate methods for improving mRNA delivery safety and specificity.
Main Methods:
- Formulation of deep eutectic-lipid nanocomposites using cholinium malonate and pre-formed LNPs.
- In vivo evaluation of mRNA expression following intramuscular injection.
- Physico-chemical characterization of the nanocomposite system.
- Assessment of LNP interactions and endosomal escape.
Main Results:
- Cholinium malonate enabled linear control over mRNA expression based on concentration.
- Local muscle mRNA expression increased by 68% with the deep eutectic solvent (DES).
- Off-target liver expression decreased by 72% using the DES-modified LNPs.
- DES incorporation into LNPs influenced endosomal escape and local interactions.
Conclusions:
- Deep eutectic-lipid nanocomposites offer a new strategy for localized mRNA expression.
- This approach enhances therapeutic efficacy and reduces systemic exposure without LNP redesign.
- The system provides a versatile platform for existing LNP formulations.
Keywords:
deep eutectic solventsdrug deliveryionic liquidslipid nanoparticlesmessenger RNAnanocompositesnanomedicines
