Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors
Name
wnan.1657.pdf
Description
Published version
Size
3.2 MB
Format
Adobe PDF
Checksum (MD5)
a35bbd6b82974e07458547db95444734
Author(s)
Dobrovolskaia, Marina A
Bathe, Mark
Date Issued
2021
Journal
Wiley Interdisciplinary Reviews / Nanomedicine and Nanobiotechnology
Publisher
Wiley
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/WNAN.1657
