Systemic mRNA Delivery to the Lungs by Functional Polyester-based Carriers

Yunfeng Yan, Hu Xiong, Xinyi Zhang, Qiang Cheng, Daniel J. Siegwart

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. We report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells. The formulation of mRNA polyplex nanoparticles (NPs) with Pluronic F127 decreased the surface charge. Although this improved the stability of mRNA nanoparticles, the delivery potency decreased with increased F127 content. Thus, we determined that NP stabilization with 5% F127 could balance the protective effects and delivery potency. 5% F127 formulated PE4K-A17-0.33C12 mRNA NPs enabled luciferase expression predominantly in the lungs after intravenous injection into mice. The efficient mRNA delivery specifically to lungs by degradable carriers suggests the potential for the treatment of pulmonary diseases.

Original languageEnglish (US)
Pages (from-to)4307-4315
Number of pages9
JournalBiomacromolecules
Volume18
Issue number12
DOIs
StatePublished - Dec 11 2017

Fingerprint

UCON 50-HB-5100
Polyesters
Messenger RNA
Nanoparticles
Luciferases
Poloxamer
Pulmonary diseases
Vaccines
Surface charge
Ether
Chlorides
Ethers
Screening
Stabilization
Lead
Genes
Proteins

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Systemic mRNA Delivery to the Lungs by Functional Polyester-based Carriers. / Yan, Yunfeng; Xiong, Hu; Zhang, Xinyi; Cheng, Qiang; Siegwart, Daniel J.

In: Biomacromolecules, Vol. 18, No. 12, 11.12.2017, p. 4307-4315.

Research output: Contribution to journalArticle

Yan, Yunfeng ; Xiong, Hu ; Zhang, Xinyi ; Cheng, Qiang ; Siegwart, Daniel J. / Systemic mRNA Delivery to the Lungs by Functional Polyester-based Carriers. In: Biomacromolecules. 2017 ; Vol. 18, No. 12. pp. 4307-4315.
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