open access publication

Article, 2022

Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections

Matter, ISSN 2590-2393, 2590-2385, Volume 5, 3, Pages 975-987, 10.1016/j.matt.2021.12.022

Contributors

Abramson, Alex [1] [2] Kirtane, Ameya R 0000-0002-3779-0363 [1] [2] [3] [4] Shi, Yunhua [1] [2] [3] [4] Zhong, Grace J 0000-0002-3784-2995 [1] [2] Collins, Joy E 0000-0002-9232-4517 [1] [2] [3] [4] Tamang, Siddartha M [1] [2] Ishida, Keiko 0000-0003-0894-296X [1] [2] Hayward, Alison M 0000-0002-9581-8563 [1] [2] [3] [4] Wainer, Jacob 0000-0002-4845-228X [1] [2] Rajesh, Netra Unni [1] [2] Lu, Xiaoya [1] [2] Gao, Yuan [1] [2] Karandikar, Paramesh V 0000-0002-3529-2037 [1] [2] Tang, Chaoyang [1] [2] Lopes, Aaron [1] [2] Wahane, Aniket V [1] [2] Reker, Daniel 0000-0003-4789-7380 [1] [3] [4] Frederiksen, Morten Revsgaard 0000-0003-0000-4426 [5] Jensen, Brian [5] Langer, Robert Samuel 0000-0003-4255-0492 (Corresponding author) [1] [2] Traverso, Giovanni (Corresponding author) [1] [2] [3] [4]

Affiliations

  1. [1] Koch Institute for Integrative Cancer Research
    2. [NORA names: United States; America, North; OECD];
  2. [2] Massachusetts Institute of Technology
    3. [NORA names: United States; America, North; OECD];
  3. [3] Brigham and Women's Hospital
    4. [NORA names: United States; America, North; OECD];
  4. [4] Harvard University
    5. [NORA names: United States; America, North; OECD];
  5. [5] Novo Nordisk (Denmark)
    6. [NORA names: Novo Nordisk; Private Research; Denmark; Europe, EU; Nordic; OECD]

Abstract

Nucleic acids are enabling a new generation of therapeutics and vaccines to treat and prevent a range of diseases. While these therapies have typically been limited to parenteral dosing, patients and clinicians prefer oral dosage forms. Furthermore, oral delivery enables local transfection of cells in the gastrointestinal tract not easily targeted via parenteral administration. To address these challenges, we synthesized and screened a library of branched hybrid poly(β-amino ester) mRNA nanoparticles for transfection efficiency; then we combined the highest performing formulations with ingestible milli-injector capsules capable of delivering formulations directly into gastric tissue. We validated the performance of formulations and devices in rodents and pigs, demonstrating protein translation in the delta, gastric, and parietal cells of the gastric mucosa, in addition to systemic uptake. We anticipate oral delivery of mRNA could facilitate rapid deployment of episodic interventions, such as vaccines, and support long-term therapies.

Keywords

acid, administration, capsule, cells, clinicians, delivering formulation, delivery, delivery of mRNA, delta, deployment, devices, disease, dosage forms, dose, efficiency, episodic interventions, form, formulation, gastric mucosa, gastric tissue, gastrointestinal tract, high-performance formulations, injection, intervention, library, local transfection, localized transfection of cells, long-term therapy, mRNA, mRNA delivery, mRNA nanoparticles, mucosa, nanoparticles, nucleic acids, oral delivery, oral dosage forms, parenteral administration, parenteral dose, parietal cells, patients, performance, performance formulation, performance of formulations, pigs, protein, protein translation, rodents, systemic uptake, therapeutics, therapy, tissue, tissue injection, tract, transfection, transfection efficiency, transfection of cells, translation, uptake, vaccine

Funders

  • Brigham and Women's Hospital
  • National Science Foundation
  • National Institute of Biomedical Imaging and Bioengineering
  • Pharmaceutical Research and Manufacturers of America

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