{"doi":"10.1016/j.mattod.2025.06.001","title":"Protein-based spherical nanoparticles for dsRNA delivery to nematodes – A platform technology for RNA silencing","abstract":"Spherical protein nanoparticles can deliver double-stranded RNA, facilitating nematode control by RNA interference. We have developed proteinaceous spherical nanoparticles (SNPs) based on tobacco mild green mosaic virus (TMGMV) by thermal shape transition, and have used them to encapsulate double-stranded RNA (dsRNA), which triggers RNA interference (RNAi). The efficacy of this approach was demonstrated in Caenorhabditis elegans , a model nematode species. SNPs were readily ingested by transgenic nematodes expressing the fluorescent reporter gene mCherry , resulting in potent gene silencing, as detected by fluorescence imaging. SNPs can help to overcome dsRNA delivery barriers in real-world situations such as targeting phytoparasitic nematodes in the soil, thus providing a new platform nanotechnology for nematode control by RNAi. Phytoparasitic nematodes are widespread agricultural pests that cause severe damage to roots, resulting in significant crop losses. Chemical control with nematicides is the conventional pest management strategy, but this is a threat to beneficial species and human health. Furthermore, indiscriminate use leads to the emergence of resistant pest populations. Phytoparasitic nematodes can also be controlled by RNA interference (RNAi), a eukaryote defense mechanism against invasive nucleic acids that is triggered by double stranded RNA (dsRNA) and causes the specific cleavage or translational repression of the corresponding mRNA. More than 75 genes in phytoparasitic nematodes have been targeted by RNAi under laboratory conditions, but the application of RNAi in the field is limited by delivery barriers such as inefficient cellular uptake and RNA degradation. The latter is particularly important when targeting soil-dwelling nematodes because free RNA is not stable in soil. We therefore encapsulated dsRNA in proteinaceous spherical nanoparticles (SNPs) formed by the thermal annealing of coat proteins from tobacco mild green mosaic virus (TMGMV). We optimized loading of dsRNA into SNPs by charge neutralization and condensation of dsRNA with Mg 2+ at pH < 3.0, allowing us to encapsulate up to 0.2 mg dsRNA per 1.0 mg of SNPs, 100–200 nm in diameter. This was a 10-fold improvement over the non-optimized dsRNA-SNP formulation (i.e. encapsulation of dsRNA without charge neutralization and condensation). A transgenic Caenorhabditis elegans line constitutively expressing mCherry was used as a model to confirm that dsRNA remains functional and triggers RNAi following the ingestion of dsRNA-laden SNPs. The silencing effect lasted ∼180 h and reduced mCherry fluorescence by 76.2 ± 13.6 %. We confirmed that dsRNA-loaded SNPs retain their silencing activity when passed through a soil column, indicating that the RNAi-based control of phytoparasitic nematodes using SNPs should be possible in the field.","journal":"Materials Today","year":2025,"id":518478,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":921901,"name":"Adam A. Caparco","orcid":"0000-0002-8545-8349","position":1,"is_corresponding":false},{"id":109245,"name":"Nicole F. Steinmetz","orcid":"0000-0002-0130-0481","position":2,"is_corresponding":false},{"id":1378239,"name":"Patrick Opdensteinen","orcid":"0000-0002-4068-0843","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:49:09.679930Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}