Description
- Abstract:
- In the last few years, and especially during the COVID-19 pandemic, gene therapy has gained tremendous momentum due to the rapid emergence and large-scale commercial production of non-viral mRNA vaccines. The Pfizer–BioNTech and Moderna lipid nanoparticle (LNP) mRNA vaccines exhibited remarkable efficacy against the SARS-CoV-2 virus and demonstrated exceptional safety in clinical trials and throughout their emergency use during the pandemic period. The success of these vaccines has showcased the potential of non-viral mRNA-based therapies to revolutionize the field of vaccine science by provoking stronger immune responses with higher specificity while limiting unfavorable inflammatory side effects that have been observed in the past from traditional viral vaccines. Despite the great achievements of the COVID-19 LNP mRNA vaccines, serious challenges remain regarding the stability of these nucleic acid delivery devices and the costs associated with the storage and distribution of these vaccines. While polymeric NPs have been proposed as an alternative, lack of efficacy and concerns about toxicity have largely limited their development. This research aims to develop a novel polymer-lipid hybrid NP platform that employs surface loading of mRNA and can be lyophilized into a shelf stable powder to increase the shelf life of vaccines that utilize these NPs as nucleic acid delivery devices. Furthermore, these NPs can be used to encapsulate therapeutic drugs thus enabling the development of dual therapy approaches in which genetic material and drugs can be co-delivered simultaneously using a single NP delivery system. This work demonstrates that these NPs can be used to safely and efficiently transfect cells with both mRNA and DNA and that both water-soluble and organic-soluble drugs can be loaded into these NPs and delivered alongside transfection. In a B16F10 tumor model in mice we demonstrated that this dual delivery approach can be used to limit tumor growth over time and improve survival. Overall, this work provides evidence for the potential of these NPs to not only overcome many of the challenges associated with current mRNA vaccine fabrication and storage techniques but also unlock a new dimension of vaccine designs through dual delivery approaches.
- Notes:
- Thesis (Sc. M.)--Brown University, 2025
Citation
Knittle, Brendan,
"LIPO-POLYMERIC NANOPARTICLES FOR SIMULTANEOUS DRUG AND GENE DELIVERY FOR THE TREATMENT OF MELANOMA"
(2025).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:3bt69dzx/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....