One of the major hurdles in RNAi research has been the development of safe and effective delivery systems for siRNAs. Although various chemical modifications have been proposed to improve their pharmacokinetic behaviour, their delivery to target cells and tissues presents many challenges. In this work, we implemented a receptor-targeting strategy to selectively deliver siRNAs to cancer cells using folic acid as a ligand. Folic acid is capable of binding to cell-surface folate receptors with high affinity. These receptors have become important molecular targets for cancer research as they are overexpressed in numerous cancers despite being expressed at low levels in normal tissues. Employing a post-column copper-catalyzed alkyne–azide cycloaddition (CuAAC), we report the synthesis of siRNAs bearing folic acid modifications at different positions within the sense strand. In the absence of a transfection carrier, these siRNAs were selectively taken up by cancer cells expressing folate receptors. We show that centrally modified folic acid–siRNAs display enhanced gene-silencing activity against an exogenous gene target (∼80% knockdown after 0.75 μM treatment) and low cytotoxicity. In addition, these siRNAs achieved potent dose-dependent knockdown of endogenous Bcl-2, an important anti-apoptotic gene.

Science communication has been increasingly viewed as a necessity and obligation of scientists in recent years. The rise of Web 2.0 technologies, such as social media, has made communication of science to the public more accessible as a whole. While one of the primary goals of science communication is to increase public engagement, there is very little research to show the type of communication that fosters the highest levels of engagement. Here we evaluate two social medial platforms, Instagram and TikTok, and assess the type of educational science content (ESC) that promotes user awareness and overall engagement. Specifically, we measured the level of engagement between static and dynamic posts on Instagram, and lecture-style and experimental videos on TikTok. User engagement is measured through the analysis of relative number of likes, comments, shares, saves, and views of each post in the various categories. We found that users interact with ESC significantly more (p<0.05) when the content is presented in dynamic ways with a component of experimentation. Together, we took the findings of this study and provided a series of suggestions for conducting science communication on social media, and the type of ESC that should be used to promote better user outcomes.

Short interfering RNAs (siRNAs) show promise as gene-silencing therapeutics, but their cellular uptake remains a challenge. We have recently shown the synthesis of siRNAs bearing a single neutral phenylethyl phosphotriester linkage within the sense strand. Here, we report the synthesis of siRNAs bearing three different hydrophobic phosphate triester linkages at key positions within the sense strand and assess their gene silencing in the absence of a transfection carrier. The best siRNAs bearing hydrophobic phosphate triester tails were not aromatic and exhibited effective gene silencing (IC50 ≈ 56–141 nM), whereas the aromatic derivative with three hydrophobic tails did not exhibit carrier-free gene silencing.

No abstract

The use of short interfering RNAs (siRNAs) as therapeutics holds great promise, but chemical modifications must first be employed to improve their pharmacokinetic properties.