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Highlights in Chemical Biology

Chemical biology news from across RSC Publishing.



Flipping lipids


07 December 2006

Mimicking enzyme flip-flops could lead to better DNA delivery vehicles for gene therapy. 

Vladimir Sidorov and colleagues at Virginia Commonwealth University, in Richmond, US, have developed a method of mimicking the flip function of flippase enzymes. Flippases, along with floppases and scramblases, belong to a family of enzymes that control lipid distribution across cell membranes. Recently, it has emerged that changing the lipid distribution could be useful in medical treatments such as gene therapy. 

Flipping lipids in liposomes could lead to improved vehicles for gene therapy

Flipping lipids in liposomes could lead to improved vehicles for gene therapy

Gene therapy often uses membranes known as liposomes - spherical lipid bilayers - to transport DNA to target cells. The liposomes contain a proportion of cationic lipids, allowing them to absorb the negatively-charged DNA. However, some of the cationic lipids are found in the outer layer of the liposome bilayer where they can interact with proteins in the blood and result in the DNA being released early. 

"The greatest challenge for this research will be to develop the lipid flip methodology to the stage where it could be used for therapeutic needs."
Sidorov has found a way to eliminate these unwanted interactions, using a flip action to transfer all the cationic lipids into the inner layer of the bilayer, making the liposome more stable in the blood. This could improve the delivery of DNA and make this type of gene therapy more effective, said Sidorov.

Sidorov made the lipids flip by creating a potential across the liposome using potassium and chloride ions. The negative pole inside the bilayer attracts the cationic lipids to the inside. 

'The greatest challenge for this research will be to develop the lipid flip methodology to the stage where it could be used for therapeutic needs,' said Sidorov. 

Sarah Dixon

References

Towards improved gene delivery: Flip of cationic lipids in highly polarized liposomes.

RG Uhl II, Amalia Stevenson and Vladimir Sidorov, Chem. Commun., 2007,


DOI: 10.1039/B611505e