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Nanoparticles Deliver siRNA with Increased Efficiency and Specificity

Recent efforts to utilize nanoparticles as delivery mechanisms in RNA interference protocols have shown great promise. Earlier this year, a group headed by researchers at MIT designed lipopeptide spheres capable of exclusively targeting hepatocytes. The spheres proved five times more effective than alternative siRNA delivery techniques. Due to the nature of the particles’ make-up, however, the effect was specific to hepatocytes.

In a paper appearing this month in “Nature Nanotechnology”, lead authors James Dahlman, a graduate student at MIT, and Carmen Barnes, a scientist at Alnylam Pharmaceuticals, describe a technique for targeting siRNA-harboring nanoparticles to endothelial cells. The particles are able to deliver the enclosed siRNA specifically to endothelial cells in several organs, including the lungs, kidneys, and heart. The particles were found to penetrate liver endothelial cells, but not hepatocytes.

The nanospheres were composed of low-molecular-weight polyamines and lipids arranged in concentric circles. The group tested approximately 2,400 variants of their particle, measuring each one’s ability to deliver sufficient siRNA to inhibit expression of a fluorescent protein. The variants displaying the greatest promise were then screened for their ability to inhibit the TIE2 gene in endothelial cells.

A very promising finding

The resulting nanoparticles are specific and highly efficient. The amount of siRNA required to inhibit expression was found to be 100 times less than what is necessary for conventional siRNA delivery methods. What’s more, the spheres could be loaded with different RNA sequences, silencing expression of up to five different genes at one time.

To illustrate the potential for clinical applications, researchers used the particles to deliver siRNA to endothelial cells in the lungs. The RNA was designed to shut off VEGF receptor 1 and Dll4, both of which are involved in the progression of lung cancer. As a result, the expression of both genes was blocked, significantly slowing tumor growth in laboratory mice.

RNA interference is a powerful technique, with possible applications ranging from the treatment of single gene disorders such as Huntington’s disease, to the inhibition of genes responsible for facilitating the progression of cancer. The ability to target siRNA delivery to specific cells is a crucial step. The research team is hopeful that their nanospheres can be utilized in the clinical setting in the near future. The study was a joint effort between scientists from MIT, Alnylam Pharmaceuticals, and Harvard Medical School. Findings have been published online ahead of print and can be viewed at Nature Nanotechnology.

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Lluis M. Martínez | SEPMAG Chief Scientific Officer

Founder of SEPMAG, Lluis holds a PhD in Magnetic Materials by the UAB. He has conducted research at German and Spanish academic institutions. Having worked in companies in Ireland, USA and Spain, he has more than 20 years of experience applying magnetic materials and sensors to industrial products and processes. He has filed several international patents on the field and co-authored more than 20 scientific papers, most of them on the subject of magnetic particle movement.

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