Computationally Designed Protein Nanoparticles for Biological Macromolecule Delivery
Abstract
Current nanoparticle technologies for drug delivery suffer from limitations of the materials from which they are constructed. Both liposomal formulations and polymer-based synthetic nanoparticles have limited functional capacities and tend to be heterogeneous, unstable in vivo, and often toxic. Proteins are ideal materials for the construction of advanced nanoscale delivery technologies as they are the most functionally sophisticated molecules known, inherently biocompatible, genetically encoded, and form highly ordered structures that can be modified with residue-level precision. However, current protein-based delivery technologies are derived from naturally occurring viruses, which are intolerant to substantial modification, present safety concerns, and are limited in their functional diversity. As a result, the development of a safe, effective, and general platform for the cytoplasmic delivery of biological molecules remains an unsolved problem. The ideal delivery system would be constructed from the bottom up with every feature tailored to the desired function. However, until recently, there were no general methods available for predictively designing new protein nanomaterials with customized structures. We developed such a method based on advanced computational protein design methodologies and demonstrated its ability to design self-assembling multi-component protein nanomaterials with atomic-level accuracy. Our long-term vision is to develop general and robust methods for designing protein-based molecular machines that can package, protect, and selectively deliver a variety of therapeutic cargoesÑsmall molecules, proteins, polymers, and various classes of nucleic acids (mRNA, DNA, siRNA, miRNA, etc.)Ñto target cell types in vivo. In essence, we believe that designed protein nanomaterials will ultimately be the solution to Òthe delivery problemÓÑone of the major challenges in modern medicine. By designing each element of these materials from the bottom up, we will enable an unprecedented level of control and customization regarding their structures and functions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 04, 2019
- Source ID
- W911NF1510645
Entities
People
- Neil P. King
Organizations
- Army Contracting Command
- Defense Advanced Research Projects Agency
- University of Washington