Intradigm uses nanoparticles and also claims successful in vivo delivery, so the following abstract may be more relevant to what we're discsussing.
>>Nucleic Acids Res. 2004 Nov 01;32(19):e149.
Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle.
Schiffelers RM, Ansari A, Xu J, Zhou Q, Tang Q, Storm G, Molema G, Lu PY, Scaria PV, Woodle MC.
Intradigm Corporation, 12115K Parklawn Drive, Rockville MD 20852, USA.
Potent sequence selective gene inhibition by siRNA 'targeted' therapeutics promises the ultimate level of specificity, but siRNA therapeutics is hindered by poor intracellular uptake, limited blood stability and non-specific immune stimulation. To address these problems, ligand-targeted, sterically stabilized nanoparticles have been adapted for siRNA. Self-assembling nanoparticles with siRNA were constructed with polyethyleneimine (PEI) that is PEGylated with an Arg-Gly-Asp (RGD) peptide ligand attached at the distal end of the polyethylene glycol (PEG), as a means to target tumor neovasculature expressing integrins and used to deliver siRNA inhibiting vascular endothelial growth factor receptor-2 (VEGF R2) expression and thereby tumor angiogenesis. Cell delivery and activity of PEGylated PEI was found to be siRNA sequence specific and depend on the presence of peptide ligand and could be competed by free peptide. Intravenous administration into tumor-bearing mice gave selective tumor uptake, siRNA sequence-specific inhibition of protein expression within the tumor and inhibition of both tumor angiogenesis and growth rate. The results suggest achievement of two levels of targeting: tumor tissue selective delivery via the nanoparticle ligand and gene pathway selectivity via the siRNA oligonucleotide. This opens the door for better targeted therapeutics with both tissue and gene selectivity, also to improve targeted therapies with less than ideal therapeutic targets.<<
For some reason, their efforts seem to have caused less of a stir than Alnylam's work, and I'm not sure why (other than the the fact that the stir can't be measured by stock price, since Intradigm is private). Perhaps Walking Shadow can help here. The diagram in the link below seems to imply injection via the tail vein, and I seem to recall that method was not supposed to translate well for humans. OTOH, it could be just the way the drew it.
intradigm.com
Cheers, Tuck |
