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Let's do the twist: Spiral proteins are efficient gene delivery agents

CHAMPAIGN, Ill. Clinical gene therapy may be one step closer, thanks to a new twist on an old class of molecules.

A group of University of Illinois researchers, led by professors Jianjun Cheng and Fei Wang, have demonstrated that short spiral-shaped proteins can efficiently deliver DNA segments to cells. The team published its work in the journal Angewandte Chemie.

"The main idea is these are new materials that could potentially be used for clinical gene therapy," said Cheng, a professor of materials science and engineering, of chemistry and of bioengineering.

Researchers have been exploring two main pathways for gene delivery: modified viruses and nonviral agents such as synthetic polymers or lipids. The challenge has been to address both toxicity and efficiency. Polypeptides, or short protein chains, are attractive materials because they are biocompatible, fine-tunable and small.

"There are very good in vitrotransfection agents available, but we cannot use them in vivo because of their toxicity or because some of the complexes are too large," Cheng said. "Using our polypeptides, we can control the size down to the 200 nanometer range, which makes it a very interesting delivery system for in vivo applications."

A polypeptide called poly-L-lysine (PLL) was an early contender in gene delivery studies. PLL has positively charged side chains molecular structures that stem from each amino acid link in the polypeptide chain so it is soluble in the watery cellular environment.

However, PLL gradually fell into disuse because of its limited ability to deliver genes to the inside of cells, a process called transfection, and its high toxicity. Cheng postulated that PLL's low efficiency could be a function of its globular shape, as polypeptides with charged side chains tend to adopt a random coil structure, instead of a more orderly spiral helix.

"We never studied the connections of conformation with

Contact: Liz Ahlberg
University of Illinois at Urbana-Champaign

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