Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We...
| Main Authors: | , , , |
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2023
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| Online Access: | https://hdl.handle.net/1721.1/150602 |
| _version_ | 1811081474044067840 |
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| author | Puigmal, Núria Ramos, Víctor Artzi, Natalie Borrós, Salvador |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Puigmal, Núria Ramos, Víctor Artzi, Natalie Borrós, Salvador |
| author_sort | Puigmal, Núria |
| collection | MIT |
| description | Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies. |
| first_indexed | 2024-09-23T11:47:15Z |
| format | Article |
| id | mit-1721.1/150602 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:47:15Z |
| publishDate | 2023 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1506022024-03-20T20:04:44Z Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination Puigmal, Núria Ramos, Víctor Artzi, Natalie Borrós, Salvador Massachusetts Institute of Technology. Institute for Medical Engineering & Science Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies. 2023-05-08T17:29:58Z 2023-05-08T17:29:58Z 2023-04-17 2023-04-27T13:50:39Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150602 Pharmaceutics 15 (4): 1262 (2023) PUBLISHER_CC http://dx.doi.org/10.3390/pharmaceutics15041262 Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Puigmal, Núria Ramos, Víctor Artzi, Natalie Borrós, Salvador Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title | Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title_full | Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title_fullStr | Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title_full_unstemmed | Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title_short | Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination |
| title_sort | poly beta amino ester s based delivery systems for targeted transdermal vaccination |
| url | https://hdl.handle.net/1721.1/150602 |
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