Extrahepatic Gene Editing In Vivo Using Organic Solvent‐Free Lipid Nanoparticles
Year: 2026
Type: article
Abstract: Targeted therapy, which modifies genes and their expression, holds great promise for treating a variety of diseases, including cancer, inborn errors of metabolism, and acute and chronic inflammatory and infectious conditions. However, it also presents challenges related to RNA delivery, immune responses, side effects of delivery vectors, and the need for individualized formulations. To overcome these limitations, the choice of lipids and formulation processes might be re-evaluated, with a focus on eliminating critical components, such as poly(ethylene glycol) (PEG) and ethanol. Thus, a purely water-based formulation for lipid nanoparticles was developed, offering a material-efficient, time-saving process with high reproducibility. Initially, a stealth lipid containing poly(2-methyl-2-oxazoline) (PMeOx) was used, and the formulation was later expanded to include approved lipids. These nanoparticles not only efficiently transfect primary human immune cells but also effectively deliver multiple nucleotides in CRISPR-Cas9 applications. Moreover, an in vivo comparison revealed that the nanoparticles exhibited preferential transfection in extrahepatic tissues. This distinguishes them from conventional cholesterol-rich lipid nanoparticles, which primarily target the liver regardless of the application route.
Source: Small
Institutions: Friedrich Schiller University Jena, Jena University Hospital, École Nationale Supérieure de Chimie de Montpellier, Centre National de la Recherche Scientifique, Université de Montpellier, Institut Charles Gerhardt Montpellier, Inserm, Institut Universitaire de France, Institute for Regenerative Medicine & Biotherapy, Center for Sepsis Control and Care
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Awards: RUBIN - ATHANA - Antifungale Therapieansätze durch nanopartikelbasierte Zielsteuerung von Wirkstoffen, TP8: Translationale Erforschung von neuen antifungalen Therapieansätzen, G1878789790, G232205927, G2529565156, Effiziente Polymer-basierte Nanotransporter durch Einbinden von biologischen Konzepten (PolyBioMik), SFB 1278: Polymerbasierte NanopartikelBibliotheken für die Entwicklung zielgerichteter antiinflammatorischer Strategien, G342014721, Gentransfer für globale Herausforderungen – Untersuchung von PolymerMembranWechselwirkungen zur Effizienzsteigerung von neuartigen Polymeren, G6007893492, Physico-chemically modified nanosized extracellular vesicles for as a bio-inspired vector for intracellular delivery of antibody fragments
OpenAlex ID: W7143662516