Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors
Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021
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| Online Access: | https://hdl.handle.net/1721.1/133503 |
| _version_ | 1811083715638460416 |
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| author | Dobrovolskaia, Marina A Bathe, Mark |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dobrovolskaia, Marina A Bathe, Mark |
| author_sort | Dobrovolskaia, Marina A |
| collection | MIT |
| description | Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with viral vectors, nonviral delivery vectors offer controlled immunogenicity and low manufacturing cost, yet suffer from limitations in toxicity, targeting, and transduction efficiency. Structured DNA assemblies fabricated using the principle of scaffolded DNA origami offer a new nonviral delivery vector with intrinsic, yet controllable immunostimulatory properties and virus-like spatial presentation of ligands and immunogens for cell-specific targeting, activation, and control over intracellular trafficking, in addition to low manufacturing cost. However, the relative utilities and limitations of these vectors must clearly be demonstrated in preclinical studies for their clinical potential to be realized. Here, we review the major capabilities, opportunities, and challenges we foresee in translating these next-generation delivery and vaccine vectors to the clinic. This article is categorized under:. Therapeutic Approaches and Drug Discovery > Emerging Technologies. Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures. Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. |
| first_indexed | 2024-09-23T12:37:39Z |
| format | Article |
| id | mit-1721.1/133503 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:37:39Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1335032023-12-19T21:33:26Z Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors Dobrovolskaia, Marina A Bathe, Mark Massachusetts Institute of Technology. Department of Biological Engineering Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with viral vectors, nonviral delivery vectors offer controlled immunogenicity and low manufacturing cost, yet suffer from limitations in toxicity, targeting, and transduction efficiency. Structured DNA assemblies fabricated using the principle of scaffolded DNA origami offer a new nonviral delivery vector with intrinsic, yet controllable immunostimulatory properties and virus-like spatial presentation of ligands and immunogens for cell-specific targeting, activation, and control over intracellular trafficking, in addition to low manufacturing cost. However, the relative utilities and limitations of these vectors must clearly be demonstrated in preclinical studies for their clinical potential to be realized. Here, we review the major capabilities, opportunities, and challenges we foresee in translating these next-generation delivery and vaccine vectors to the clinic. This article is categorized under:. Therapeutic Approaches and Drug Discovery > Emerging Technologies. Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures. Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. 2021-10-27T19:53:12Z 2021-10-27T19:53:12Z 2021 2021-08-24T18:36:46Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133503 en 10.1002/WNAN.1657 Wiley Interdisciplinary Reviews / Nanomedicine and Nanobiotechnology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Dobrovolskaia, Marina A Bathe, Mark Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title | Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title_full | Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title_fullStr | Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title_full_unstemmed | Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title_short | Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors |
| title_sort | opportunities and challenges for the clinical translation of structured dna assemblies as gene therapeutic delivery and vaccine vectors |
| url | https://hdl.handle.net/1721.1/133503 |
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