POS8-0906
Hydrophobic modification of mRNA for enhancing lipid nanoparticles (LNPs)-mediated mRNA delivery efficiency
Topic
S8. Frontiers of Functional Polymers in Biology and Medicine
When and Where
Sep 30, 2026
08:30 - 09:30
Room 301 (Grand Ballroom)
Session Chairs
Heesuk KIM
Jinhye BAE
Presenter(s)
Choeun Park (Korea University)
Co-Author(s)
Abstract
Lipid nanoparticles (LNPs) are a highly promising delivery method primarily used for delivering nucleic acids, proteins, peptides, and other therapeutic agents. This technology is being used as a key technology in mRNA therapeutics, including COVID-19 vaccines.
However, a drawback of LNPs system is that a larger amount of lipid components is delivered into our body along with the mRNA, raising concerns about potential side effects caused by lipid components. To address this issue, several studies are currently underway to reduce the amount of lipid components delivered.
Here, we introduce a novel form of hydrophobically modified mRNA that incorporates hydrophobic moiety into the mRNA molecule. This innovative approach involves the introduction of a DNA oligo with cholesterol or alkyl groups attached to the 3' end of the mRNA. By using hydrophobically modified mRNA, we aim to reduce the lipid ratio in mRNA-LNP formulations while enhancing the delivery efficiency of the mRNA. This strategy is expected to improve both the safety and efficiency of mRNA therapeutics.
As a result, hydrophobically modified mRNA demonstrates enhanced efficiency in encapsulation into LNPs and protein expression compared to conventional mRNA, particularly under formulation conditions with a significantly lower mRNA-to-lipid ratio. These results demonstrate that hydrophobically modified mRNA allows for significantly enhanced mRNA delivery efficiency with a minimized requirement for lipid components, while preserving particle stability.
Therefore, hydrophobically modified mRNA is expected to mitigate issues related to lipid accumulation in the body by reducing the amount of lipid required, thereby enhancing the long-term safety of treatments. Furthermore, this approach has potential as an applicable method for lipid nanoparticle-mediated therapeutics.
However, a drawback of LNPs system is that a larger amount of lipid components is delivered into our body along with the mRNA, raising concerns about potential side effects caused by lipid components. To address this issue, several studies are currently underway to reduce the amount of lipid components delivered.
Here, we introduce a novel form of hydrophobically modified mRNA that incorporates hydrophobic moiety into the mRNA molecule. This innovative approach involves the introduction of a DNA oligo with cholesterol or alkyl groups attached to the 3' end of the mRNA. By using hydrophobically modified mRNA, we aim to reduce the lipid ratio in mRNA-LNP formulations while enhancing the delivery efficiency of the mRNA. This strategy is expected to improve both the safety and efficiency of mRNA therapeutics.
As a result, hydrophobically modified mRNA demonstrates enhanced efficiency in encapsulation into LNPs and protein expression compared to conventional mRNA, particularly under formulation conditions with a significantly lower mRNA-to-lipid ratio. These results demonstrate that hydrophobically modified mRNA allows for significantly enhanced mRNA delivery efficiency with a minimized requirement for lipid components, while preserving particle stability.
Therefore, hydrophobically modified mRNA is expected to mitigate issues related to lipid accumulation in the body by reducing the amount of lipid required, thereby enhancing the long-term safety of treatments. Furthermore, this approach has potential as an applicable method for lipid nanoparticle-mediated therapeutics.
