RNA interference is a powerful method for the knockdown of pathologically relevant genes. Small interfering RNAs (siRNAs) have been widely demonstrated as effective biomedical genetic-therapy applications for many diseases. Unfortunately, siRNA duplexes are not ideal drug-like molecules. Problems hindering their effective application fundamentally lie in their delivery, stability, and off-target effects. Delivery systems provide solutions to many of the challenges facing siRNA therapeutics. Due to some fatal disadvantages of viral vectors, nonviral carriers have been studied extensively. Aside from liposomes, nanoparticles and cationic polymer carriers have exhibited improved in vivo stability, better biocompatibility, and efficiency for gene silencing with less cellular toxicity. They may represent a promising strategy for siRNA-based therapies, especially as nanomaterials. The present review also summarizes other methods of siRNA delivery and the side effects of the nanoparticles.
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http://dx.doi.org/10.2147/IJN.S17040 | DOI Listing |
Viruses
December 2024
Division of Plant Pathology, Indian Agricultural Research Institute, New Delhi 110012, India.
The increasing challenges posed by plant viral diseases demand innovative and sustainable management strategies to minimize agricultural losses. Exogenous double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) represents a transformative approach to combat plant viral pathogens without the need for genetic transformation. This review explores the mechanisms underlying dsRNA-induced RNAi, highlighting its ability to silence specific viral genes through small interfering RNAs (siRNAs).
View Article and Find Full Text PDFPharmaceutics
January 2025
Integrative Health and Environmental Analysis Research Laboratory, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, 1117 Budapest, Hungary.
Cyclodextrins can serve as carriers for various payloads, utilizing their capacity to form unique host-guest inclusion complexes within their cavity and their versatile surface functionalization. Recently, cationic cyclodextrins have gained considerable attention, as they can improve drug permeability across negatively charged cell membranes and efficiently condense negatively charged nucleic acid due to electrostatic interactions. This review focuses on state-of-the-art and recent advances in the construction of cationic cyclodextrin-based delivery systems.
View Article and Find Full Text PDFPharmaceutics
January 2025
Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. In this study, we introduce a novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) and siRNA targeting TNF-α (si) using microfluidic technology, marking the first use of such a combination for RA therapy.
View Article and Find Full Text PDFPharmaceutics
December 2024
Department of Pharmaceutical Technology, Faculty of Natural Sciences I, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle/Saale, Germany.
Background/objectives: Bringing small interfering RNA (siRNA) into the cell cytosol to achieve specific gene silencing is an attractive but also very challenging option for improved therapies. The first step for successful siRNA delivery is the complexation with a permanent cationic or ionizable compound. This protects the negatively charged siRNA and enables transfection through the cell membrane.
View Article and Find Full Text PDFLife (Basel)
January 2025
Laboratory of Toxicology and Risk Assessment, Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, 20133 Milan, Italy.
Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns-particularly those specific to this class of drugs-is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs.
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