Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders
Viruslike particles (VLPs) fabricated using wireframe DNA origami are emerging as promising vaccine and gene therapeutic delivery platforms due to their programmable nature that offers independent control over their size and shape, as well as their site-specific functionalization. As materials that...
| Κύριοι συγγραφείς: | , , , , , , , , , |
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| Άλλοι συγγραφείς: | |
| Μορφή: | Άρθρο |
| Γλώσσα: | English |
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American Chemical Society (ACS)
2023
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| Διαθέσιμο Online: | https://hdl.handle.net/1721.1/147761 |
| _version_ | 1826213032233009152 |
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| author | Wamhoff, Eike-Christian Romanov, Anna Huang, Hellen Read, Benjamin J Ginsburg, Eric Knappe, Grant A Kim, Hyun Min Farrell, Nicholas P Irvine, Darrell J Bathe, Mark |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Wamhoff, Eike-Christian Romanov, Anna Huang, Hellen Read, Benjamin J Ginsburg, Eric Knappe, Grant A Kim, Hyun Min Farrell, Nicholas P Irvine, Darrell J Bathe, Mark |
| author_sort | Wamhoff, Eike-Christian |
| collection | MIT |
| description | Viruslike particles (VLPs) fabricated using wireframe DNA origami are emerging as promising vaccine and gene therapeutic delivery platforms due to their programmable nature that offers independent control over their size and shape, as well as their site-specific functionalization. As materials that biodegrade in the presence of endonucleases, specifically DNase I and II, their utility for the targeting of cells, tissues, and organs depends on their stability in vivo. Here, we explore minor groove binders (MGBs) as specific endonuclease inhibitors to control the degradation half-life of wireframe DNA origami. Bare, unprotected DNA-VLPs composed of two-helix edges were found to be stable in fetal bovine serum under typical cell culture conditions and in human serum for 24 h but degraded within 3 h in mouse serum, suggesting species-specific endonuclease activity. Inhibiting endonucleases by incubating DNA-VLPs with diamidine-class MGBs increased their half-lives in mouse serum by more than 12 h, corroborated by protection against isolated DNase I and II. Our stabilization strategy was compatible with the functionalization of DNA-VLPs with HIV antigens, did not interfere with B-cell signaling activity of DNA-VLPs in vitro, and was nontoxic to B-cell lines. It was further found to be compatible with multiple wireframe DNA origami geometries and edge architectures. MGB protection is complementary to existing methods such as PEGylation and chemical cross-linking, offering a facile protocol to control DNase-mediated degradation rates for in vitro and possibly in vivo therapeutic and vaccine applications. |
| first_indexed | 2024-09-23T15:42:15Z |
| format | Article |
| id | mit-1721.1/147761 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:42:15Z |
| publishDate | 2023 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1477612024-01-19T21:12:40Z Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders Wamhoff, Eike-Christian Romanov, Anna Huang, Hellen Read, Benjamin J Ginsburg, Eric Knappe, Grant A Kim, Hyun Min Farrell, Nicholas P Irvine, Darrell J Bathe, Mark Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Ragon Institute of MGH, MIT and Harvard Viruslike particles (VLPs) fabricated using wireframe DNA origami are emerging as promising vaccine and gene therapeutic delivery platforms due to their programmable nature that offers independent control over their size and shape, as well as their site-specific functionalization. As materials that biodegrade in the presence of endonucleases, specifically DNase I and II, their utility for the targeting of cells, tissues, and organs depends on their stability in vivo. Here, we explore minor groove binders (MGBs) as specific endonuclease inhibitors to control the degradation half-life of wireframe DNA origami. Bare, unprotected DNA-VLPs composed of two-helix edges were found to be stable in fetal bovine serum under typical cell culture conditions and in human serum for 24 h but degraded within 3 h in mouse serum, suggesting species-specific endonuclease activity. Inhibiting endonucleases by incubating DNA-VLPs with diamidine-class MGBs increased their half-lives in mouse serum by more than 12 h, corroborated by protection against isolated DNase I and II. Our stabilization strategy was compatible with the functionalization of DNA-VLPs with HIV antigens, did not interfere with B-cell signaling activity of DNA-VLPs in vitro, and was nontoxic to B-cell lines. It was further found to be compatible with multiple wireframe DNA origami geometries and edge architectures. MGB protection is complementary to existing methods such as PEGylation and chemical cross-linking, offering a facile protocol to control DNase-mediated degradation rates for in vitro and possibly in vivo therapeutic and vaccine applications. 2023-01-27T18:08:43Z 2023-01-27T18:08:43Z 2022 2023-01-27T15:31:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147761 Wamhoff, Eike-Christian, Romanov, Anna, Huang, Hellen, Read, Benjamin J, Ginsburg, Eric et al. 2022. "Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders." ACS Nano, 16 (6). en 10.1021/ACSNANO.1C11575 ACS Nano Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Wamhoff, Eike-Christian Romanov, Anna Huang, Hellen Read, Benjamin J Ginsburg, Eric Knappe, Grant A Kim, Hyun Min Farrell, Nicholas P Irvine, Darrell J Bathe, Mark Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title | Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title_full | Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title_fullStr | Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title_full_unstemmed | Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title_short | Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders |
| title_sort | controlling nuclease degradation of wireframe dna origami with minor groove binders |
| url | https://hdl.handle.net/1721.1/147761 |
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