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Peer-reviewedCC BYACS nano

Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic Therapy.

  • Abdulraouf M Abbas1,2
  • Ramy Ghanim3
  • Sebastian Rudden1
  • David Schultz3
  • Bora Jang1
  • Avraham Shakked1
  • Hyejin Kim1
  • James E Dahlman1
  • Alex Abramson1,3,4,5
5 affiliations
  1. 1Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, Georgia30332, United States.
  2. 2Emory Global Diabetes Research Center of the Woodruff Health Sciences Center and Emory University, Atlanta, Georgia30322, United States.
  3. 3School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia30332, United States.
  4. 4Wearable Intelligent Systems and Healthcare Center, Institute for Matters and Systems, Georgia Institute of Technology, Atlanta, Georgia30332, United States.
  5. 5Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia30332, United States.
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Abstract

Lipid nanoparticles (LNPs) administered parenterally often show poor localization to multiple tissue types, including the pancreas and gastrointestinal (GI) tract. Furthermore, patients typically prefer orally administered drugs to those that are given parenterally. We therefore investigated whether GI LNP administration to buccal, gastric, small intestinal, colonic, and rectal submucosal tissues could simultaneously circumvent parenteral administration while enhancing LNP delivery to previously inaccessible locations. We found that, in addition to local targeting, gastric LNP administration achieved an order of magnitude greater pancreas delivery in rodents than intravenous administration. Gastric dosing of glucagon-like peptide-1 mRNA also improved blood glucose regulation in mice compared with phosphate-buffered saline controls. Additionally, we found that buccal LNP administration targeted local and lymphatic tissues. Furthermore, dosing mice with ovalbumin mRNA resulted in equivalent immunoglobulin G blood titers to those of intramuscular delivery. These results suggest that GI administration can reprogram LNP biodistribution, expanding therapeutic opportunities for both local and systemic nucleic acid delivery.

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Cite

BibTeXRIS
BibTeX
@article{abbas2026targeted,
  title = {{Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic Therapy.}},
  author = {Abdulraouf M Abbas and Ramy Ghanim and Sebastian Rudden and David Schultz and Bora Jang and Avraham Shakked and Hyejin Kim and James E Dahlman and Alex Abramson},
  journal = {ACS nano},
  year = {2026},
  month = oct,
  doi = {10.1021/acsnano.5c18549},
  url = {https://europepmc.org/article/MED/42917207},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic Therapy.
AU  - Abdulraouf M Abbas
AU  - Ramy Ghanim
AU  - Sebastian Rudden
AU  - David Schultz
AU  - Bora Jang
AU  - Avraham Shakked
AU  - Hyejin Kim
AU  - James E Dahlman
AU  - Alex Abramson
PY  - 2026
DA  - 2026/10/01
JO  - ACS nano
DO  - 10.1021/acsnano.5c18549
UR  - https://europepmc.org/article/MED/42917207
AB  - Lipid nanoparticles (LNPs) administered parenterally often show poor localization to multiple tissue types, including the pancreas and gastrointestinal (GI) tract. Furthermore, patients typically prefer orally administered drugs to those that are given parenterally. We therefore investigated whether GI LNP administration to buccal, gastric, small intestinal, colonic, and rectal submucosal tissues could simultaneously circumvent parenteral administration while enhancing LNP delivery to previously inaccessible locations. We found that, in addition to local targeting, gastric LNP administration achieved an order of magnitude greater pancreas delivery in rodents than intravenous administration. Gastric dosing of glucagon-like peptide-1 mRNA also improved blood glucose regulation in mice compared with phosphate-buffered saline controls. Additionally, we found that buccal LNP administration targeted local and lymphatic tissues. Furthermore, dosing mice with ovalbumin mRNA resulted in equivalent immunoglobulin G blood titers to those of intramuscular delivery. These results suggest that GI administration can reprogram LNP biodistribution, expanding therapeutic opportunities for both local and systemic nucleic acid delivery.
SN  - 1936-0851
SN  - 1936-086X
ER  -