It is shown that the exchange properties of the imino and hydroxyl protons of polyuridilic acid (poly(rU)) allow use of this compound as a chemical-exchange saturation transfer (CEST) contrast agent. A proton/proton sensitivity enhancement factor of over 5000 per imino proton allowed the detection of a few micromolar of polymer (2000 uridine units; 644 kD) with a 50% change in the water signal. The enhancement factor would increase further at even lower concentrations, opening up the submicromolar range. When poly(rU) was complexed to a dendrimer carrying 250 positive charges, the stoichiometry was approximately one RNA for 10 dendrimers. The sensitivity enhancement was reduced but remained large (2300/imino proton), bringing enhanced CEST visibility to the dendrimers. The net charge of the complex was positive, suggesting that the complexed dendrimers would still interact with cell membranes, and that the RNA-dendrimer complex could provide a model for a gene delivery system with good CEST visibility.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/mrm.10463 | DOI Listing |
Sci Adv
January 2025
Thomas Lord Department of Mechanical Engineering and Materials, Duke University, Durham, NC 27708, USA.
Precise and rapid disease detection is critical for controlling infectious diseases like COVID-19. Current technologies struggle to simultaneously identify viral RNAs and host immune antibodies due to limited integration of sample preparation and detection. Here, we present acoustofluidic integrated molecular diagnostics (AIMDx) on a chip, a platform enabling high-speed, sensitive detection of viral immunoglobulins [immunoglobulin A (IgA), IgG, and IgM] and nucleic acids.
View Article and Find Full Text PDFSci Transl Med
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.
View Article and Find Full Text PDFPLoS Biol
January 2025
Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized.
View Article and Find Full Text PDFPLoS One
January 2025
Integrative Multiomics Lab, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Background: Rheumatoid arthritis (RA) is a degenerative autoimmune disease, often managed through symptomatic treatment. The co-occurrence of the reported extra-articular comorbidities such as inflammatory bowel disease (IBD), and dementia may complicate the pathology of the disease as well as the treatment strategies. Therefore, in our study, we aim to elucidate the key genes, and regulatory elements implicated in the progression and association of these diseases, thereby highlighting the linked potential therapeutic targets.
View Article and Find Full Text PDFEnviron Sci Technol
January 2025
School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang 212013, China.
Organophosphorus pesticides (OPs) pose significant environmental and health risks, and their detoxification through catalytic hydrolysis using zirconium-based metal-organic frameworks (Zr-MOFs) has attracted considerable interest due to the strong Lewis acid metal ions. Albeit important, the defects of the materials for OP hydrolysis (e.g.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!