TY  - JOUR
AB  - Non-coding RNAs (ncRNAs) like microRNAs (miRNAs) or small interference RNAs (siRNAs) with their power to selectively silence any gene of interest enable the targeting of so far 'undruggable' proteins and diseases. Such RNA molecules have gained much attention from biotech and pharmaceutical companies, which led to the first Food and Drug Administration (FDA) approved ncRNA therapeutic in 2018.However, the main barrier in clinical practice of ncRNAs is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver them to specific tissues and cell types, and release them into the cytoplasm of the targeted cells, all without inducing adverse effects.For that reason, drug delivery approaches, formulations, technologies and systems for transporting pharmacological ncRNA compounds to achieve a diagnostic or therapeutic effect in the human body are in demand.Here, we review the development of therapeutic lipid -based nanoparticles for delivery of miRNAs, one class of endogenous ncRNAs with specific regulatory functions. We outline challenges and opportunities for advanced miRNA-based therapies, and discuss the complexity associated with the delivery of functional miRNAs. Novel strategies are addressed how to deal with the most critical points in miRNA delivery, such as toxicity, specific targeting of disease sites, proper cellular uptake and endosomal escape of miRNAs. Current fields of application and various preclinical settings involving miRNA therapeutics are discussed, providing an outlook to future clinical approaches.Following the current trends and technological developments in nanomedicine exciting new delivery systems for ncRNA-based therapeutics can be expected in upcoming years.
AU  - Scheideler, M.
AU  - Vidakovic, I.*
AU  - Prassl, R.*
C1  - 57362
C2  - 47757
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Lipid nanocarriers for microRNA delivery.
JO  - Chem. Phys. Lipids
VL  - 226
PB  - Elsevier Ireland Ltd
PY  - 2020
SN  - 0009-3084
ER  - 

TY  - JOUR
AB  - Sphingolipids are important lipids and integral members of membranes, where they form small microdomains called lipid rafts, These rafts are enriched in cholesterol and sphingolipids, which influences biophysical properties. Interestingly, the membranes of the biomedical model organism Caenorhabditis elegans contain only low amounts of cholesterol. Sphingolipids in C. elegans are based on an unusual Cl7iso branched sphingoid base. In order to analyze and the sphingolipidome of C. elegans in more detail, we performed fractionation of lipid extracts and depletion of glycero- and glycerophospholipids together with in-depth analysis using UPLC-UHRToF-MS. In total we were able to detect 82 different sphingolipids from different classes, including several isomeric species.
AU  - Hänel, V.
AU  - Pendleton, C.
AU  - Witting, M.
C1  - 55947
C2  - 46664
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
SP  - 15-22
TI  - The sphingolipidome of the model organism Caenorhabditis elegans.
JO  - Chem. Phys. Lipids
VL  - 222
PB  - Elsevier Ireland Ltd
PY  - 2019
SN  - 0009-3084
ER  - 

TY  - JOUR
AB  - A detailed understanding of biomembrane architecture is still a challenging task. Many in vitro studies have shown lipid domains but much less information is known about the lateral organization of membrane proteins because their hydrophobic nature limits the use of many experimental methods. We examined lipid domain formation in biomimetic Escherichia coli membranes composed of phosphatidylethanolamine and phosphatidylglycerol in the absence and presence of 1% and 5% (mol/mol) membrane multidrug resistance protein, EmrE. Monolayer isotherms demonstrated protein insertion into the lipid monolayer. Subsequently, Brewster angle microscopy was applied to image domains in lipid matrices and lipid-protein mixtures. The images showed a concentration dependent impact of the protein on lipid domain size and shape and more interestingly distinct coexisting protein clusters. Whereas lipid domains varied in size (14-47μm), protein clusters exhibited a narrow size distribution (2.6-4.8μm) suggesting a non-random process of cluster formation. A 3-D display clearly indicates that these proteins clusters protrude from the membrane plane. These data demonstrate distinct co-existing lipid domains and membrane protein clusters as the monofilm is being compressed and illustrate the significant mutual impact of lipid-protein interactions on lateral membrane architecture.
AU  - Gröger, T.
AU  - Nathoo, S.*
AU  - Ku, T.*
AU  - Sikora, C.*
AU  - Turner, R.J.*
AU  - Prenner, E.J.*
C1  - 7291
C2  - 29651
SP  - 216-224
TI  - Real-time imaging of lipid domains and distinct coexisting membrane protein clusters.
JO  - Chem. Phys. Lipids
VL  - 165
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 0009-3084
ER  -