UK chemists have used smart polymers to deliver DNA into cells. Based on pH-sensitive poly(ethylene glycol) (PEG) lipids, the polymers can be used as a removable protective coat for gene delivery systems. 

Gene delivery systems, or vectors, have to protect their DNA cargo from enzymes, cross cell membranes and yet still release a therapeutic dose of intact DNA inside the target cell. Viral vectors can deliver genes into cells, however, they can provoke an immune response which limits their therapeutic use. One of the problems often associated with non-viral gene delivery systems is that 'the efficiency is too low and that the vectors are not sufficiently stable, particularly in vivo,' says Helen Hailes a reader in chemical biology at University College London, UK.

To overcome this problem, Hailes and her colleagues have developed acid-cleavable PEG lipids to shield the DNA in a non-viral vector. The vector consists of a targeting peptide and cargo DNA with the PEG lipids as covering. This coating stabilises the particles, protects the DNA from nuclease enzymes, provides water solubility and facilitates transport through the cell membrane. Once the vector is inside the cell, the lower pH triggers hydrolysis and shedding of the coating, releasing the cargo DNA. As different PEG lipid structures are hydrolysed at different pH, this offers a method of controlling the pH dependence of DNA release, suggests Hailes.

The PEG (yellow) shields the DNA until it is removed by acid cleavage at the linker site (blue)

The team demonstrated the new system's effectiveness by transferring DNA coding a bioluminescent enzyme into different cell types, and measuring the enzyme's activity. 'The PEG lipids seem to provide cell specific properties,' comments Antonio Villaverde, an expert in non-viral gene therapy at the Autonomous University of Barcelona, Spain. 'This could be an interesting element to favour cell targeting in delivering such constructs.'

Looking to the future, Hailes says that the team hopes to 'design different tunable features into the lipids for a range of delivery applications.' She adds that this could include using the system to deliver small interfering RNA - short strands of RNA that can be used to interfere with gene expression.  

Russell Johnson