Assessment of Nanoparticle Assemblies for Efficient Gene Therapy Vehicles
Abstract
The delivery of nucleic acids including siRNA, mRNA and CRISPR gene editing complexes represents a major challenge for the clinical translation of gene therapy. Polymer-, lipid nanoparticle- or virus-based platforms have been explored extensively but have not been able to achieve the safe and efficient delivery profiles. As an alternative strategy, we have developed techniques to design and synthesize DNA and RNA nanoparticles based on the DNA origami technique that provide unique opportunities for the loading of nucleic acid cargo. We are seeking to translate the delivery platform from an academic setting into commercial ventures. Key advantages of the nucleic acid-based nanoparticles include full synthetic control (1) over the chemical and structural composition of the delivery platform and (2) over functionalization valency, spacing and stoichiometry including the exterior attachment of targeting modalities for applications to cancer as well as genetic and infectious diseases and the interior attachment of cargo with (3) ideal synergy with siRNA, mRNA and CRISPR/Cas9 gene editing complexes. Major goals of this project are (1) the identification of key partners in the biotechnological industry and of promising therapeutic applications and (2) understanding the technical challenges of our nucleic acid-based nanoparticles and competing delivery platforms. This report will focus on these technical challenges in the context of pre-clinical development. Key questions include the immunotoxicity of nucleic acid-based nanoparticles and their biodistribution in animal models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 09, 2021
- Accession Number
- AD1208089
Entities
People
- Mark Bathe
- Tyson R. Shepherd
Organizations
- Massachusetts Institute of Technology