Conversational Agents in Organisations: Strategic Applications and Implementation Considerations

Conversational agents (CAs) promise to create significant organisational value, by transforming how organisations operate and serve customers. Yet, the malleability of this technology poses challenges to both researchers and practitioners because of the wide range of strategic applications they can enable. Drawing on the lens of routine capability, this study investigates strategic applications of CAs, and their associated implementation enablers and challenges. Via an exploratory case study of eight organisations that have successfully implemented CAs, this paper contributes to the literature on the value and implementation of conversational agents in particular and cognitive technologies in general by developing a typology of CA strategic applications and their implementation considerations. For practitioners, the findings highlight the interplay between technology, user, and project management factors that need to be addressed to ensure the successful delivery of the value of CAs

Boosting Intracellular Delivery of Lipid Nanoparticle-Encapsulated mRNA

Intracellular delivery of mRNA holds great potential for vaccine− and therapeutic discovery and development. Despite increasing recognition of the utility of lipid-based nanoparticles (LNPs) for intracellular delivery of mRNA, particle engineering is hindered by insufficient understanding of endosomal escape, which is believed to be a main limiter of cytosolic availability and activity of the nucleic acid inside the cell. Using a series of CRISPR-based genetic perturbations of the lysosomal pathway, we have identified that late endosome/lysosome (LE/Ly) formation is essential for functional delivery of exogenously presented mRNA. Lysosomes provide a spatiotemporal hub to orchestrate mTOR signaling and are known to control cell proliferation, nutrient sensing, ribosomal biogenesis, and mRNA translation. Through modulation of the mTOR pathway we were able to enhance or inhibit LNP-mediated mRNA delivery. To further boost intracellular delivery of mRNA, we screened 212 bioactive lipid-like molecules that are either enriched in vesicular compartments or modulate cell signaling. Surprisingly, we have discovered that leukotriene-antagonists, clinically approved for treatment of asthma and other lung diseases, enhance intracellular mRNA delivery in vitro (over 3-fold, <i>p</i> < 0.005) and in vivo (over 2-fold, <i>p</i> < 0.005). Understanding LNP-mediated intracellular delivery will inspire the next generation of RNA therapeutics that have high potency and limited toxicity