NU 2011-123

Inventors

Yves Ruff

Samuel I. Stupp*

Short Description

A method of making self-assembled nanostructures for improved gene and siRNA delivery.

Background

The use of peptides for the protection and delivery of nucleic acids is a well-established field. Molecular self-assembly has evolved in its capacity to design increasingly complex delivery structures using peptides such as one-dimensional nanofibers, nanobelts, ribbons or helices, all of which are not accessible using traditional synthesis methods. A critical limitation of self-assembled nanostructures is the lack of control over dispersity characteristics such as the size, shape and mass, compared to closed systems like self-assembled nanocages, limiting their usefulness.

Abstract

Researchers at Northwestern University have developed a method that successfully encapsulates double-stranded DNA with preassembled mushroom-shaped nanostructures. These structures present themselves as monodispersed filamentous virus-like particles which enable gene delivery in a biomimetic fashion. The nanostructures aim to mimic the capsid proteins, or capsomers of natural filamentous viruses like the tobacco mosaic virus (TMV) by creating artificial capsomers from self-assembled peptides conjugated to poly(ethylene glycol) (PEG). The researchers determined that a high molecular weight of PEG segments was critical for the formation of monodispersed and uniformly shaped virus-like complexes. They achieved excellent control over both the morphology and dimensions of the complexes by optimizing the molecular design of the monomeric peptides. Their novel method of controlling the length of filamentous virus-like particles enables further control of nanostructural characteristics such as permeability, polyvalency, and extended circulation times in biological systems. Varying these features may be fine-tuned for the design of future therapies and materials.

Applications

• Non-viral artificial nucleic acid vectors for in vivo gene delivery
• Non-viral artificial nucleic acid vectors for in vivo siRNA delivery
• Targeted in vivo anti-metastatic or pro-apoptotic gene delivery to tumors
• Preparation of monodisperse virus like one-dimensional nanostructures with electronic properties

Advantages

• Targeted DNA delivery without using viruses but rather virus-like materials
• Tunable characteristics like permeability, polyvalency, and extended circulation times in biological systems
• May be coupled to other molecules such as a small molecule, an antibody, an enzyme, a structural polypeptide or hormone
• May serve as templates or building blocks for more complex structures

Publication

Ruff Y, Moyer T, Newcomb CJ, Demeler B, Stupp, SI (2013) Precision Templating with DNA of a Virus Like Particle with Peptide Nanostructures. Journal of the American Chemical Society, 135; 6211-6219.

IP Status

Issued US Patent No. 9,650,421