Promising Agents For Gene Delivery | December 19, 2011 Issue - Vol. 89 Issue 51 | Chemical & Engineering News
Volume 89 Issue 51 | p. 10 | News of The Week
Issue Date: December 19, 2011

Promising Agents For Gene Delivery

Molecular Biology: Helical cationic peptides bring genes to cells efficiently
Department: Science & Technology
News Channels: Biological SCENE
Keywords: gene delivery, genetic engineering, cationic helical peptides
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Complex (top) of gene (brown helix) and helical cationic peptides (green) enters cells via endocytosis. The peptides’ charge and helicity later promote endosome swelling and rupture, permitting DNA cargo to enter the cell.
Credit: Courtesy of Jianjun Cheng
Complex gene and helical cationic peptides enters cells via endocytosis.
 
Complex (top) of gene (brown helix) and helical cationic peptides (green) enters cells via endocytosis. The peptides’ charge and helicity later promote endosome swelling and rupture, permitting DNA cargo to enter the cell.
Credit: Courtesy of Jianjun Cheng

A new class of helical charged peptides could make it easy to deliver modified genes to cells for research and gene therapy.

Bionanomaterials specialist Jianjun Cheng of the University of Illinois, Urbana-Champaign, and coworkers designed and synthesized the peptides and show that they deliver genes to cells more efficiently than do other nonviral agents (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201104262). They believe the peptides will also prove to be safer than viruses.

Viruses are the most efficient gene-delivery agents. But because viruses cause immune reactions and other safety risks, scientists are seeking substitutes.

These efforts have included modifying viruses to reduce side effects and developing nonviral agents like cationic lipids, peptides, and polymers. Clinical success has been limited, and no gene-delivery system has yet been approved for clinical use.

Cheng and coworkers’ new peptides have positively charged amine groups on extended side chains, which permit them to adopt helical shapes that aid gene delivery. The positive charges enable the peptides to readily bind DNA, which is negatively charged, and form complexes that enter cells via endocytosis. The peptides’ charge and helicity eventually promote swelling and rupture of the resulting endosomes, allowing the DNA cargo to escape into the cytosol and find its way to the nucleus.

Cheng and coworkers say the helical cationic peptides deliver genes up to several orders of magnitude more efficiently than the widely studied cationic gene-delivery agents polyethyleneimine, Lipofectamine, and polylysine, and with similar or reduced toxicity.

Gene-delivery specialist Suzie Hwang Pun of the University of Washington, Seattle, says she believes the study “will instigate a new train of thought for designing materials for gene delivery.”

Nanobiotechnologist Jordan J. Green of Johns Hopkins University adds that “all viral and nonviral gene-delivery agents evaluated clinically thus far are insufficient.” The new study “opens up a whole new library of biomaterials for nonviral gene delivery,” although further safety and efficacy testing of the new peptide agents is still needed.

 
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