29 April 2008

Polymer shell for gene delivery

CHEMPORT.RUBritish chemists used "smart" polymers to deliver DNA molecules to cells.

Polymer materials created using pH-sensitive polyethylene glycol (PEG) lipids can be used as a double protective shell for gene delivery systems.

Gene delivery systems (vectors) must protect the transferred DNA molecule from the action of enzymes, pass through the cell membrane and release DNA inside the target cell. Virus-based vectors can deliver genes inside cells, but at the same time they can cause an immune response of the cell. The problem associated with non-viral gene delivery methods is the low efficiency of such systems and the low stability of vectors.

PEG (yellow) protects the DNA molecule until it is removed by acid hydrolysis of the linker (blue). (Drawing from Mol. BioSyst., 2008; DOI: 10.1039/b719782a)

To overcome these problems, Helen Hailes, a specialist in chemical biology from the University of London College of Medicine, has developed acid-degradable lipids based on PEG to screen DNA in a non-viral vector.

The vector consists of a "target designator" peptide, a load of DNA and a protective shell of PEG lipids.

Such a shell stabilizes the particles, protecting DNA from nuclease enzymes, provides solubility in water and simplifies transport through the cell membrane. When the vector enters the cell, a low pH value promotes hydrolysis and destruction of the coating, releasing the transferred DNA molecule. Due to the fact that different PEG lipids are hydrolyzed at different pH values, it becomes possible to control the release of DNA by controlling pH.

The researchers demonstrated the effectiveness of the new transfer system by transfecting DNA molecules encoding the synthesis of bioluminescent protein into various cell types.

Portal "Eternal youth" www.vechnayamolodost.ru29.04.2008

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