{"doi":"10.1073/pnas.2215091120","title":"Molecular DNA dendron vaccines","abstract":"A foundational principle of rational vaccinology is that vaccine structure plays a critical role in determining therapeutic efficacy, but in order to establish fundamental, effective, and translatable vaccine design parameters, a highly modular and well-defined platform is required. Herein, we report a DNA dendron vaccine, a molecular nanostructure that consists of an adjuvant DNA strand that splits into multiple DNA branches with a varied number of conjugated peptide antigens that is capable of dendritic cell uptake, immune activation, and potent cancer killing. We leveraged the well-defined architecture and chemical modularity of the DNA dendron to study structure-function relationships that dictate molecular vaccine efficacy, particularly regarding the delivery of immune-activating DNA sequences and antigenic peptides on a single chemical construct. We investigated how adjuvant and antigen placement and number impact dendron cellular uptake and immune activation, in vitro. These parameters also played a significant role in raising a potent and specific immune response against target cancer cells. By gaining this structural understanding of molecular vaccines, DNA dendrons successfully treated a mouse cervical human papillomavirus TC-1 cancer model, in vivo, where the vaccine structure defined its efficacy; the top-performing design effectively reduced tumor burden (<150 mm 3 through day 30) and maintained 100% survival through 44 d after tumor inoculation.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":335884,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"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":1066330,"name":"John P. Cavaliere","orcid":null,"position":1,"is_corresponding":false},{"id":868706,"name":"Michelle H. Teplensky","orcid":"0000-0003-4664-420X","position":2,"is_corresponding":false},{"id":269712,"name":"Michael Evangelopoulos","orcid":"0000-0002-5300-4289","position":3,"is_corresponding":false},{"id":79412,"name":"Chad A. Mirkin","orcid":"0000-0002-6634-7627","position":4,"is_corresponding":false},{"id":868707,"name":"Max E. Distler","orcid":"0000-0002-3750-5075","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:10:02.777338Z","pmid":"36696444","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":[]}