PLGA-PEG-Azide from PolySciTech used in development of nanoparticles for delivery of SiRNA delivery system

 

Silencing RNA has the ability to act as a selective gene expression modifier, turning off or negating the effect of specific gene expression on demand. This can be a useful tool for a wide range of disease states however suffers from several drawbacks including SiRNA’s susceptibility to degradation which makes delivery of it to cells difficult. Researchers at Northwestern University used PLGA-PEG-Azide (cat# AI085) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop particles for delivery of SiRNA to cells. This research holds promise to improve SiRNA delivery. Read more: Park, Jungsoo, Michael Evangelopoulos, Matthew Kuo Vasher, Sergej Kudruk, Namrata Ramani, Vinzenz Mayer, Alexander Carlos Solivan, Andrew Lee, and Chad Alexander Mirkin. "Enhancing Endosomal Escape and Gene Regulation Activity for Spherical Nucleic Acids." Small (2023): 2306902. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202306902

“The therapeutic potential of small interfering RNAs (siRNAs) is limited by their poor stability and low cellular uptake. When formulated as spherical nucleic acids (SNAs), siRNAs are resistant to nuclease degradation and enter cells without transfection agents with enhanced activity compared to their linear counterparts; however, the gene silencing activity of SNAs is limited by endosomal entrapment, a problem that impacts many siRNA-based nanoparticle constructs. To increase cytosolic delivery, SNAs are formulated using calcium chloride (CaCl2) instead of the conventionally used sodium chloride (NaCl). The divalent calcium (Ca2+) ions remain associated with the multivalent SNA and have a higher affinity for SNAs compared to their linear counterparts. Importantly, confocal microscopy studies show a 22% decrease in the accumulation of CaCl2-salted SNAs within the late endosomes compared to NaCl-salted SNAs, indicating increased cytosolic delivery. Consistent with this finding, CaCl2-salted SNAs comprised of siRNA and antisense DNA all exhibit enhanced gene silencing activity (up to 20-fold), compared to NaCl-salted SNAs regardless of sequence or cell line (U87-MG and SK-OV-3) studied. Moreover, CaCl2-salted SNA-based forced intercalation probes show improved cytosolic mRNA detection.”