{"doi":"10.1002/adhm.202301515","title":"Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering","abstract":"The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T cell activity in the tumor microenvironment. While clinical approaches to inhibiting the PD-1 pathway using antibody blockade have been broadly successful, these approaches lead to widespread PD-1 suppression, increasing the risk of autoimmune reactions. This study reports the development of an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient gene knockdown in T cells. In developing this platform, interesting interactions are observed between the two RNA cargoes when co-encapsulated, leading to improved expression and knockdown characteristics compared to delivering either cargo alone. This messenger RNA (mRNA)/small interfering RNA (siRNA) co-delivery platform is adopted to deliver chimeric antigen receptor (CAR) mRNA and siRNA targeting PD-1 to primary human T cells ex vivo and strong CAR expression and PD-1 knockdown are observed without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation for a number of immunoengineering applications, including the development of improved cancer immunotherapies.","journal":"Advanced Healthcare Materials","year":2023,"id":316692,"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":95,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":615522,"name":"Kelsey L. Swingle","orcid":"0000-0001-8475-9206","position":1,"is_corresponding":false},{"id":1017826,"name":"Ryann A. Joseph","orcid":"0000-0002-0795-6094","position":2,"is_corresponding":false},{"id":6599,"name":"David Mai","orcid":"0000-0002-9238-0164","position":3,"is_corresponding":false},{"id":240732,"name":"Ningqiang Gong","orcid":"0000-0002-9444-8505","position":4,"is_corresponding":false},{"id":103471,"name":"Margaret M. Billingsley","orcid":"0000-0003-4499-9066","position":5,"is_corresponding":false},{"id":231967,"name":"Mohamad‐Gabriel Alameh","orcid":"0000-0002-5672-6930","position":6,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":7,"is_corresponding":false},{"id":618835,"name":"Neil C. Sheppard","orcid":"0000-0002-9551-9491","position":8,"is_corresponding":false},{"id":227870,"name":"Carl H. June","orcid":"0000-0003-0241-3557","position":9,"is_corresponding":false},{"id":103470,"name":"Michael J. Mitchell","orcid":"0000-0002-3628-2244","position":10,"is_corresponding":false},{"id":632576,"name":"Alex G. Hamilton","orcid":"0000-0002-9810-5630","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"37602495","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":[]}