Small interfering RNA

Recent Findings on small interfering RNA

• A structure-optimization study examined whether modifying the terminal base of the antisense strand could improve siRNA performance. The investigators hypothesized that rational extension or shortening of this terminal region would increase predicted AGO2 binding affinity, promote RISC assembly, and reduce incorporation of the sense strand. The work focused on improving targeted MMP7 gene silencing and illustrates how siRNA sequence and duplex architecture can be engineered in addition to optimizing delivery systems 42612768Aug.

• A metabolically targeted nanoplatform was designed for combination treatment of tumors. The system co-assembled a disulfide-containing amphiphilic peptide with DSPE-PEG2k-FA and co-delivered siRNA against monocarboxylate transporter 4 (siMCT4), the fatty-acid β-oxidation inhibitor Etomoxir, and the photosensitizer chlorin e6 (Ce6). This approach combined gene silencing with metabolic intervention and photodynamic therapy, linking siRNA activity to tumor vulnerability, reactive oxygen species generation, and cytotoxicity 42398835Jul.

• In hepatocellular carcinoma, a study investigated the role of the pseudogene FTH1P7 in ferroptosis evasion and sorafenib resistance. To counter this resistance mechanism, the researchers developed a nanoliposome carrying both sorafenib and FTH1P7-targeting siRNA, termed SR-siFTH1P7-LIP. The design exemplifies co-delivery of a conventional anticancer drug and siRNA to combine pharmacological treatment with suppression of a resistance-associated transcript 42546831Aug.

• An ultrasound-programmable extracellular-vesicle system was developed for colorectal cancer metastasis. The system, designated US-EV, co-delivered the sonosensitizer hematoporphyrin monomethyl ether (HMME) and siRNA targeting the N6-methyladenosine RNA-binding protein YTHDF1. The reported therapeutic concept combined ultrasound-responsive treatment with gene silencing and was associated with induction of immunogenic cell death, integrating immune effects with epigenetic or post-transcriptional pathway modulation 42309466Jun.

• A placental delivery study addressed preeclampsia by targeting multiple anti-angiogenic mediators in invasive trophoblasts. The investigators designed a dual-target divalent siRNA intended to enhance molecular stability and silence two targets simultaneously. Selective delivery was pursued with a ligand-functionalized, membrane-fusogenic liposomal system called iMFlip, directed toward receptors highly expressed in invasive trophoblasts. This work extends siRNA design from single-gene knockdown toward coordinated regulation of pathogenic pathways in a defined human cell population 42385857Jul.

• A sequential treatment platform was investigated for hepatitis B virus (HBV). The system used HBV-specific siRNA delivered by macrophage membranes that had been pre-activated with HBV-related cues, followed by photothermal ablation using aggregation-induced-emission agents. The study therefore combined antiviral gene silencing with a temporally subsequent physical therapy in a macrophage-membrane-coated nanoplatform 42709589Sep.

• Delivery of siRNA into primary human bronchial airway cells was investigated using polymeric nanoparticles. The study reflects the use of siRNA as a tool for reducing cellular protein expression in a relevant pulmonary cell model and addresses the delivery barrier that limits application of nucleic acids to airway tissues 42572107Aug.

• Partially glycosylated fourth-generation poly(propylene imine) dendrimers were evaluated as carriers for siRNA directed against the PAX3-FOXO1 fusion oncogene in alveolar rhabdomyosarcoma. This work placed dendriplex-based delivery within a cancer gene-silencing strategy targeting a disease-associated fusion transcript 42425239Jul.

• A review of peptide-mediated siRNA delivery traced the development of peptide-based systems from early designs to newer delivery platforms. It characterized siRNA therapeutics as a means of using RNAi to silence disease-associated genes, including targets implicated in diseases that are difficult to address with small molecules or antibodies. The review represents the delivery-focused direction of the field, alongside lipid, polymeric, dendrimer, and extracellular-vesicle approaches 42541443Aug.

• A lipid nanoparticle was developed to support ferroptosis-based cancer therapy by integrating a ferrous-supply-regenerating function with RNAi. The study used siRNA in the context of iron-dependent ferroptosis, a treatment strategy involving reactive oxygen species, glutathione depletion or redox imbalance, and lipid peroxidation. This represents a combination approach in which gene silencing is used to increase tumor susceptibility to ferroptotic cell death 42528415Jul.

• Collectively, these publications extend the dominant theme of therapeutic siRNA delivery. The work spans sequence optimization for AGO2 engagement, peptide and polymeric carriers, lipid nanoparticles and liposomes, dendriplexes, extracellular vesicles, and membrane-derived systems. Across cancer, HBV infection, airway-cell delivery, and preeclampsia, siRNA is being paired with metabolic inhibitors, sorafenib, sonosensitizers, photodynamic or photothermal agents, and ferroptosis-inducing strategies. Common experimental objectives include selective gene silencing, reduced tumor-cell proliferation or viability, modulation of migration and immune responses, and enhancement of therapeutic efficacy; methods used in this research area include western blotting, immunofluorescence, flow cytometry, and cytotoxicity analysis.