Next Article in Journal
Influence of Lenvatinib on the Functional Reprogramming of Peripheral Myeloid Cells in the Context of Non-Medullary Thyroid Carcinoma
Next Article in Special Issue
Nanobiotechnology-Enabled mRNA Stabilization
Previous Article in Journal
Alternative Pharmacokinetic Metrics in Single-Dose Studies to Ensure Bioequivalence of Prolonged-Release Products at Steady State—A Case Study
Previous Article in Special Issue
Protein Transduction Domain-Mediated Delivery of Recombinant Proteins and In Vitro Transcribed mRNAs for Protein Replacement Therapy of Human Severe Genetic Mitochondrial Disorders: The Case of Sco2 Deficiency
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Pharmaceutics
Volume 15
Issue 2
10.3390/pharmaceutics15020410
pharmaceutics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers

by
Huijing Wang
1,†,
Xin Liu
2,†,
Xuefeng Ai
3,
K. C. Remant-Bahadur
4,
Teo A. Dick
4,
Bingqian Yan
1,
Tingting Lu
1,
Xingliang Zhou
3,
Runjiao Luo
3,
Minglu Liu
3,
Xiangying Wang
1,
Kaixiang Li
3,
Wei Wang
3,
Hasan Uludag
4,5,6,* and
Wei Fu
1,7,*
1
Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai 200127, China
2
Department of Dental Materials, Shanghai Biomaterials Research & Testing Center, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No. 427, Jumen Rd., Shanghai 200011, China
3
Department of Pediatric Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
4
Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 2R3, Canada
5
Department of Biomedical Engineering, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
6
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada
7
Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2023, 15(2), 410; https://doi.org/10.3390/pharmaceutics15020410
Submission received: 18 November 2022 / Revised: 10 January 2023 / Accepted: 17 January 2023 / Published: 26 January 2023
(This article belongs to the Special Issue mRNA-Based Protein Replacement Therapy)
Browse Figures
Review Reports Versions Notes

Abstract

Chemically modified mRNA (modRNA) has proven to be a versatile tool for the treatment of various cancers and infectious diseases due to recent technological advancements. However, a safe and effective delivery system to overcome the complex extracellular and intracellular barriers is required in order to achieve higher therapeutic efficacy and broaden clinical applications. Here, we explored All-Fect and Leu-Fect C as novel transfection reagents derived from lipopolymers, which demonstrated excellent biocompatibility, efficient delivery capabilities, and a robust ability to escape the lysosomes. These properties directly increase mRNA stability by preventing mRNA degradation by nucleases and simultaneously promote efficient gene translation in vitro and in vivo. The modRNA delivered with lipopolymer vectors sustained effective transfection in mouse hearts following direct intramyocardial injection, as well as in major organs (liver and spleen) after systemic administration. No observable immune reactions or systemic toxicity were detected following the systemic administration of lipopolymer-mRNA complexes to additional solid organs. This study identified commercial reagents for the effective delivery of modRNA and may help facilitate the advancement of gene-based interventions involving the safe and effective delivery of nucleic acid drug substances.
Keywords: modRNA; lipopolymers; biocompatibility; lysosomal escape; effective transfection modRNA; lipopolymers; biocompatibility; lysosomal escape; effective transfection
Graphical Abstract

Share and Cite

MDPI and ACS Style

Wang, H.; Liu, X.; Ai, X.; Remant-Bahadur, K.C.; Dick, T.A.; Yan, B.; Lu, T.; Zhou, X.; Luo, R.; Liu, M.; et al. Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers. Pharmaceutics 2023, 15, 410. https://doi.org/10.3390/pharmaceutics15020410

AMA Style

Wang H, Liu X, Ai X, Remant-Bahadur KC, Dick TA, Yan B, Lu T, Zhou X, Luo R, Liu M, et al. Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers. Pharmaceutics. 2023; 15(2):410. https://doi.org/10.3390/pharmaceutics15020410

Chicago/Turabian Style

Wang, Huijing, Xin Liu, Xuefeng Ai, K. C. Remant-Bahadur, Teo A. Dick, Bingqian Yan, Tingting Lu, Xingliang Zhou, Runjiao Luo, Minglu Liu, and et al. 2023. "Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers" Pharmaceutics 15, no. 2: 410. https://doi.org/10.3390/pharmaceutics15020410

APA Style

Wang, H., Liu, X., Ai, X., Remant-Bahadur, K. C., Dick, T. A., Yan, B., Lu, T., Zhou, X., Luo, R., Liu, M., Wang, X., Li, K., Wang, W., Uludag, H., & Fu, W. (2023). Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers. Pharmaceutics, 15(2), 410. https://doi.org/10.3390/pharmaceutics15020410

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop