Alan Sabirsh

Defining Composition–Cytokine Relationships Enables the Design of Lipid Nanoparticles with Programmed Immunogenicity

Adam Alexander Walters, Belal I. Hanafy, Chuan‐en Lu, Sara Marelli et autres

Lipid nanoparticles (LNPs) are central to next-generation vaccines, yet candidate selection remains largely empirical, limiting early identification of formulations associated with rare adverse events such as myocarditis. A better understanding of LNP composition-immunogenicity relationships is therefore critical for rational vaccine design. Here, …

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The Impact of Polyethylene Glycol Lipid Anchors on the Physicochemical Properties, Protein Corona, Function, and Biodistribution of Lipid Nanoparticles

Chuan‐en Lu, Kai Liu, Audrey Gallud, Viktoriia Meklesh et autres

When introduced into biological systems, the function and biodistribution of lipid nanoparticles (LNPs) are affected by the biomolecular coronas they acquire. Corona composition is determined by the biophysical and chemical properties of the particles and the contents of the biofluids. Polyethylene glycol …

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The kinetics of endosomal disruption reveal differences in lipid nanoparticle induced cellular toxicity

Stephanie M. Bates, Vítor Trovisco, Sara G. T. Pereira, S. Shea Miller et autres

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RNA encoded peptide barcodes enable efficient in vivo screening of RNA delivery systems

Uchechukwu Odunze, Nitin Rustogi, Paul N. Devine, Lorraine K. Miller et autres

Lipid nanoparticles (LNPs) have been demonstrated to hold great promise for the clinical advancement of RNA therapeutics. Continued exploration of LNPs for application in new disease areas requires identification and optimization of leads in a high throughput way. Currently available high throughput …

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Reply to: Technical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications

Kai Liu, Elisa Lázaro‐Ibáñez, Michael Lerche, Daniel Lindén et autres

The purpose of our publication “Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function” 1 was to elucidate why plasma from obese rats seemed to improve the function of therapeutic lipid nanoparticles (LNP), and use …

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TECPR1 is activated by damage‐induced sphingomyelin exposure to mediate noncanonical autophagy

Namrita Kaur, Laura Rodríguez de la Ballina, Håvard Styrkestad Haukaas, Maria Lyngaas Torgersen et autres

Cells use noncanonical autophagy, also called conjugation of ATG8 to single membranes (CASM), to label damaged intracellular compartments with ubiquitin-like ATG8 family proteins in order to signal danger caused by pathogens or toxic compounds. CASM relies on E3 complexes to sense membrane …

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Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function

Kai Liu, Ralf G. Nilsson, Elisa Lázaro‐Ibáñez, Hanna Duàn et autres

In terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased screening workflow. First, …

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Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles

Morag Rose Hunter, Lili Cui, Benjamin T. Porebski, Sara G. T. Pereira et autres

Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mechanism of lipid nanoparticle (MC3-LNP) delivery …

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Precise and systematic end group chemistry modifications on PAMAM and poly(l-lysine) dendrimers to improve cytosolic delivery of mRNA

Fanny Joubert, Alan Sabirsh, R. England, Martin Hemmerling et autres

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A Peptide Barcode Based Approach for Efficient in vivo Screening of RNA Delivery Systems

Uchechukwu Odunze, Nitin Rustogi, Paul N. Devine, Lorraine K. Miller et autres

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Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion

Nima Aliakbarinodehi, Audrey Gallud, Mokhtar Mapar, Emelie Wesén et autres

Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of mRNA therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed …

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SimSearch: A Human-in-The-Loop Learning Framework for Fast Detection of Regions of Interest in Microscopy Images

Ankit Gupta, Alan Sabirsh, Carolina Wählby, Ida‐Maria Sintorn

OBJECTIVE: Large-scale microscopy-based experiments often result in images with rich but sparse information content. An experienced microscopist can visually identify regions of interest (ROIs), but this becomes a cumbersome task with large datasets. Here we present SimSearch, a framework for quick and …

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