Development of a Structural Nucleic Acid Delivery Vector Technology

The delivery of biomacromolecules such as proteins and nucleic acids to specific cells inside the body remains a critical challenge in contemporary biomedical research. Delivery technologies to accomplish this are ideally safe, effective, versatile, and scalable, but the current commercial technologies often fall short of these characteristics. Nucleic acid nanoparticles, which are computationally-designed nanostructured assemblies of nucleic acid, represent a promising foundational technology to utilize in delivery applications. Here, I present several advancements towards developing a delivery platform designed on nucleic acid nanoparticles. After introducing the current challenges in delivery and the current commercial technologies, I detail why nucleic acid nanoparticles offer promise as components of a delivery technology. Then, I describe my thesis work on evaluating the safety of nucleic acid nanoparticles in pre-clinical animal models, on their fabrication with a focus on integrating new chemistries and characterization techniques, and on a proof-of-concept demonstration in using nucleic acid nanoparticles to deliver viral antigens in a vaccine formulation. Finally, I summarize where I think the state of the technology is today, where its potential could reach, and what the path to reach that potential is.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemical Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Knappe, Grant Alexander

Advisors dc:contributor.advisor

• Bathe, Mark
• Hammond, Paula T.

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright retained by author(s)

Licence dc:rights.uri

• https://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/155323

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/155323