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서희원Hee-Won Suh

Yale University

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Sci. Transl. Med., Aug 16 2023, 15 (709) | https://doi.org/10.1126/scitranslmed.abq0603 Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination.

Alexandra Suberi ¹, Molly K Grun ², Tianyang Mao ³, Benjamin Israelow ^3,4, Melanie Reschke ⁵, Julian Grundler⁶, Laiba Akhtar ², Teresa Lee¹, Kwangsoo Shin ¹, Alexandra S Piotrowski-Daspit ¹, Robert J Homer ⁷, Akiko Iwasaki ^3,8, Hee-Won Suh ^1*, W Mark Saltzman^1,2,9,10*

¹Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.

²Department of Chemical and Environmental Engineering, Yale University, New Haven, CT 06511, USA.

³Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.

⁴Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06519, USA.

⁵Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

⁶Department of Chemistry, Yale University, New Haven, CT 06511, USA.

⁷Department of Pathology, Yale University School of Medicine, CT 06510, USA.

⁸Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

⁹Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.

¹⁰Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA.

^*Corresponding authors: Hee-Won Suh, W. Mark Saltzman

Abstract

An inhalable platform for messenger RNA (mRNA) therapeutics would enable minimally invasive and lung-targeted delivery for a host of pulmonary diseases. Development of lung-targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here, we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine- co-ester) (PACE) polyplexes for mRNA delivery using end-group modifications and polyethylene glycol. These polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for severe acute respiratory syndrome coronavirus 2 and found that intranasal vaccination with spike protein-encoding mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected susceptible mice from lethal viral challenge. Together, these results demonstrate the translational potential of PACE polyplexes for therapeutic delivery of mRNA to the lungs.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-10-18)
연구진국외 연구진
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