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Genetic Engineering Publications - GEG Tech top picks
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Neutralizing the RNA phosphodiester backbone enables delivery of siRNA across cell membranes.
BigField GEG Tech's insight:
The authors design the synthesis of short interfering ribonucleic neutrals (siRNNs) whose phosphate backbone contains neutral phosphotriester groups, allowing for delivery into cells. Once inside cells, siRNNs are converted by cytoplasmic thioesterases into native, charged phosphodiester-backbone siRNAs, which induce robust RNAi responses. geg-tech.com 
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Challenges in the delivery of small interfering RNA (siRNA) have hampered clinical translation. Polymeric or periodic short hairpin RNAs (p-shRNAs) are a recent development that can potentially address these delivery barriers by showing improved stability and complexation to enable nanoparticle packaging. Here The scientists modify these biomacromolecules packaging via structural and sequence engineering coupled with selective enzymatic digestion to generate an open-ended p-shRNA (op-shRNA) that is cleaved over ten times more efficiently to yield siRNA. The op-shRNA induces considerably greater gene silencing than p-shRNA in multiple cancer cell lines up to nine days. Op-shRNA provides an RNAi platform that can potentially be packaged and delivered efficiently to disease sites with higher therapeutic efficacy.