Self-Assembling Nanococcoons Mimic Natural Viruses

Researchers have designed peptides, short chains of amino acids, that spontaneously package DNA into tiny capsules that could offer a new route for drug delivery or gene transport

SYNTHETIC SHELL: Engineered peptides encapsulate DNA into a nanococoon (right) that resembles parapoxvirus particles (left). Credit: Jan Mast, Lien Demeestere (left); Ying Chau (right)

Scientists have designed short peptides that self-assemble with DNA to form viruslike capsules (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja507833x). These nanococoons could offer a new route to transport genes or small-molecule drugs into cells, the researchers say.

When developing the new particles, Ying Chau and Rong Ni of Hong Kong University of Science and Technology tried to mimic how virus proteins encapsulate their genomic DNA. Viruses use simple protein units that assemble along their DNA, like a stack of Legos, she says.

So Chau and Ni set out to make a 16-amino acid peptide with three essential functions of viral proteins: remain stable in water, bind DNA, and assemble on their own. They did this by including a known DNA-binding region at one end and a water-soluble sequence at the other. The central portion of the peptide was a short, hydrophobic -sheet derived from amyloid-, the peptide linked to Alzheimers disease.

When incubated with DNA, the peptides stack up to form ribbons along the length of the DNA. These ribbons link up laterally into ellipsoid capsules between 12 and 65 nm in length, similar to the structure of a parapoxvirus. The nanococoons have stripes spaced 4 nm apart formed by the repeating -sheet folds.

By drawing inspiration from nature, the researchers have made innovative delivery particles, says Jayakumar Rajadas of Stanford University. The self-assembly is both beautiful and impressive, he says. Getting two macromolecules such as a peptide and DNA to come together, he explains, can be difficult because entropy favors the components remaining apart. Other researchers have engineered more complex proteins to assemble with DNA, but those molecules are difficult to synthesize compared with these small nanococoon peptides.

But the same factors that make the peptides efficient at self-assembly might also lead to problems in human cells, Rajadas says. For example, the amyloid -peptides are extremely good at clustering, so it may be difficult to unpack the nanococoons to deliver their contents within a cell. Also the nanococoons are resistant to enzymatic digestion. This may lead them to accumulate and form toxic clumps that sequester other proteins, lipids, or DNA. He thinks the researchers could try getting around these problems by replacing the troubling amyloid- peptide with other -sheet-containing peptides, such as silk fibroin. Finally, Rajadas points out that engineered peptides of this length tend to induce adverse immune reactions.

Nonetheless, Rajadas says, the fact that the nanococoons successfully self-assemble opens up tons of possibilities.

This article is reproduced with permission from Chemical & Engineering News ( American Chemical Society). The article was first published on November 21, 2014.

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Self-Assembling Nanococcoons Mimic Natural Viruses