A wide variety of chemical building blocks and synthetic strategies have been investigated. Specific methods have produced interesting new materials, but a single general approach for fabricating materials having many different architectures and symmetries has not emerged. This invention provides a general and predictable method for engineering self-assembling nanomaterials by combining naturally symmetric protein components.

INNOVATION:  A general strategy is described for designing proteins that self-assemble in vivo into large symmetrical nanomaterials, including molecular cages, filaments, layers, and porous materials. In this method, two unrelated proteins that naturally oligomerize are fused genetically, separated only by a short, relatively rigid linker, to form a fusion protein.

To illustrate, one molecule of protein A, which naturally forms a self-assembling oligomer, A(n), is fused rigidly to one molecule of protein B, which forms another self-assembling oligomer, B(m). The result is a fusion protein, A-B, which self assembles with other identical copies of itself into a designed nanohedral particle or material, (A-B)(p). The strategy, encompassed in U.S. patent 6,756,039, is demonstrated through the design, production, and characterization of two fusion proteins: a 49-kDa protein designed to assemble into a cage approximately 15 nm across, and a 44-kDa protein designed to assemble into long filaments approximately 4 nm wide. This general strategy for controlled self-assembly of biopolymeric materials opens the way to create a wide variety of protein-based materials with potential applications in materials science and medicine.

A modification to the patented method is an improved fusion protein that is predicted to self-assemble into a layer one protein molecule thick, extending essentially indefinitely in two dimensions. This novel nanomaterial may find utility in filtration, nanopatterning, microarrays, and immobilizing enzymes.

POTENTIAL APPLICATIONS 

1. Cage-like assemblies formed by the patented method might be useful as molecular delivery vehicles. For example, the assemblies may be used to deliver drugs or display vaccine antigens.

2. The assemblies formed by the patented method might be used to encapsulate enzymes active only against substrates that can effectively access the interior volume of such assemblies (substrate-specific catalysis).

3. The 2-D monolayers formed using a modified version of the patented method may be used as:

a. A coating material;
b. A substrate for the attachment of specific chemical groups at ultra high density;
c. A porous material for filtration with precise pore sizes on the mid nanometer scale

ADVANTAGES

1. The chemical diversity of proteins allows a wide range of materials to be generated. It is possible incorporate domains that with metal or ligand-sensitive conformations to form materials that will assemble and disassemble in response to a signal.

2. There is significant combinatorial power from connecting multiple protein components.

3. An assembly can be highly modular and can incorporate the following:

a. An addition/deletion/substitution of amino acids; and,
b. An additional protein domain providing an active site, a binding site for ligands, a site for specific chemical modification, or an antigenic epitope.

4. The protein domains are easy to manipulate genetically.

Related Papers (Selected) J Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2217-21. Epub 2001 Feb 20. Nanohedra: using symmetry to design self assembling protein cages, layers, crystals, and filaments. more... Curr Opin Struct Biol. 2002 Aug;12(4):464-70. Designing supramolecular protein assemblies. more...

Reference: UCLA Case No. 1999-246

US Patent Number: 6,756,039