Molecular buckets that pack DNA into nanoparticles could have implications for gene therapy, say scientists in Greece.

Konstantina Yannakopoulou at the National Center for Scientific Research 'Demokritos' in Athens and her team have made a series of cyclic sugars, called cyclodextrins, that can interact with DNA. Cyclodextrins have a cone-like structure that allows them to act as hosts for guest molecules. This new class of cyclodextrin can compress DNA guests into nanoparticles, which is a requirement for transferring DNA into cells, said Yannakopoulou. 

Molecular buckets that pack DNA into nanoparticles could have implications for gene therapy

DNA transfer is of particular interest in the field of gene therapy. Cyclodextrin-based gene transfer agents are likely to be more biocompatible, less toxic and cause fewer unwanted immune responses than other agents used in gene transfer, said Yannakopoulou.

Yannakopoulou's team made the novel cyclodextrins by introducing guanidine groups, the basic group of the amino acid arginine, into the sides of cyclodextrins. Yannakopoulou suggested that the incorporated guanidines interact with the phosphate groups of a DNA guest molecule. This results in a change in the charge on the DNA molecule, leading to the change in its structure, she said. 

'The circular, rigid shape of the guanidinylated cyclodextrin has an area comparable to the cross-section of alpha helices,' said Yannakopoulou. These shapes are found in arginine-rich proteins responsible for densely packing DNA, she explained.

Katherine Davies