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January 11, 2011

DNA directly put into the cell nucleus using protein nanodisks

Researchers have demonstrated that the peptide R9, formed by a specific type of amino-acid (arginine), can encapsulate genetic material, assemble itself with other identical molecules to form nanoparticles and enter directly into the cell nucleus to release the material it contains. The nanoparticles have the shape of a disk, with a diameter measuring 20 nanometres and a height of 3 nm.



The study was published recently in the journals Biomaterials and Nanomedicine and describes how scientists studied the performance of R9 nanodisks in the interior of the cells using confocal microscopy techniques provided by the UAB Microscopy Service and applied by Dr Mònica Roldán. The images show that once the cell membrane is passed, particles travel directly to the nucleus at a rate of 0.0044 micrometres per second, ten times faster than if they dispersed passively in the interior. Nanoparticles accumulate in the interior of the nucleus and not in the cytoplasm - the thick liquid between the cell membrane and nucleus - and therefore increase their level of effectiveness

The discovery represents a new category of nanoparticles offering therapeutic benefits. According to Dr Esther Vázquez, director of the project, "nanodisks assemble automatically, move rapidly, remain stable and travel to the interior of the nucleus. This makes them a promising tool as a prototype for the safe administration of nucleic acids and functional proteins.

Protein nanodisk assembling and intracellular trafficking powered by an arginine-rich (R9) peptide. Nanomedicine 5: 259-268.

RESULTS: A deep nanoscale examination of R9-powered constructs reveals a novel and promising feature of R9, that when fused to a scaffold green fluorescent protein, promote its efficient self-assembling as highly stable, regular disk-shaped nanoparticles of 20 x 3 nm. These constructs are efficiently internalized in mammalian cells and rapidly migrate through the cytoplasm towards the nucleus in a fully bioactive form. Besides, such particulate platforms accommodate, condense and deliver plasmid DNA to the nucleus and promote plasmid-driven transgene expression.

CONCLUSION: The architectonic properties of arginine-rich peptides at the nanoscale reveal a new category of protein nanoparticles, namely nanodisks, and provide novel strategic concepts and architectonic tools for the tailored construction of new-generation artificial viruses for gene therapy and drug delivery.


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