Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections
Name
1-s2.0-S2590238521006809-main.pdf
Description
Published version
Size
2.74 MB
Format
Adobe PDF
Checksum (MD5)
52779e2d4e52b311aaf1c6ae7f2f8d43
Author(s)
Abramson, Alex
Kirtane, Ameya R.
Shi, Yunhua
Zhong, Grace
Collins, Joy E.
Tamang, Siddartha
Ishida, Keiko
Hayward, Alison
Wainer, Jacob
Rajesh, Netra Unni
Date Issued
March 2022
Journal
Matter
Publisher
Elsevier BV
Citation
Abramson, Alex, Kirtane, Ameya R., Shi, Yunhua, Zhong, Grace, Collins, Joy E. et al. 2022. "Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections." Matter, 5 (3).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Division of Comparative Medicine
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.matt.2021.12.022
