{"doi":"10.1016/j.ymthe.2023.02.012","title":"Protein expression/secretion boost by a novel unique 21-mer cis-regulatory motif (Exin21) via mRNA stabilization","abstract":"Boosting protein production is invaluable in both industrial and academic applications. We discovered a novel expression-increasing 21-mer cis-regulatory motif (Exin21) that inserts between SARS-CoV-2 envelope (E) protein-encoding sequence and luciferase reporter gene. This unique Exin21 (CAACCGCGGTTCGCGGCCGCT), encoding a heptapeptide (QPRFAAA, designated as Qα), significantly (34-fold on average) boosted E production. Both synonymous and nonsynonymous mutations within Exin21 diminished its boosting capability, indicating the exclusive composition and order of 21 nucleotides. Further investigations demonstrated that Exin21/Qα addition could boost the production of multiple SARS-CoV-2 structural proteins (S, M, and N) and accessory proteins (NSP2, NSP16, and ORF3), and host cellular gene products such as IL-2, IFN-γ, ACE2, and NIBP. Exin21/Qα enhanced the packaging yield of S-containing pseudoviruses and standard lentivirus. Exin21/Qα addition on the heavy and light chains of human anti-SARS-CoV monoclonal antibody robustly increased antibody production. The extent of such boosting varied with protein types, cellular density/function, transfection efficiency, reporter dosage, secretion signaling, and 2A-mediated auto-cleaving efficiency. Mechanistically, Exin21/Qα increased mRNA synthesis/stability, and facilitated protein expression and secretion. These findings indicate that Exin21/Qα has the potential to be used as a universal booster for protein production, which is of importance for biomedicine research and development of bioproducts, drugs, and vaccines.","journal":"Molecular Therapy","year":2023,"id":358204,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"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":1108694,"name":"A. Sami Sarıbaş","orcid":null,"position":1,"is_corresponding":false},{"id":640657,"name":"Jinbiao Liu","orcid":"0000-0001-9379-6594","position":2,"is_corresponding":false},{"id":505332,"name":"Yuan Lin","orcid":"0000-0002-9879-4341","position":3,"is_corresponding":false},{"id":350577,"name":"Brittany Bodnar","orcid":"0000-0003-0467-5219","position":4,"is_corresponding":false},{"id":1096433,"name":"Ruotong Zhao","orcid":null,"position":5,"is_corresponding":false},{"id":724715,"name":"Qian Guo","orcid":"0000-0003-4655-4888","position":6,"is_corresponding":false},{"id":903428,"name":"Julia Ting","orcid":null,"position":7,"is_corresponding":false},{"id":640661,"name":"Zhengyu Wei","orcid":"0000-0002-0001-1231","position":8,"is_corresponding":false},{"id":1108695,"name":"Aidan Ellis","orcid":null,"position":9,"is_corresponding":false},{"id":103706,"name":"Fang Li","orcid":"0000-0002-1958-366X","position":10,"is_corresponding":false},{"id":337596,"name":"Xu Wang","orcid":"0000-0001-8428-9339","position":11,"is_corresponding":false},{"id":1108333,"name":"Xiaofeng Yang","orcid":"0000-0002-0828-0807","position":12,"is_corresponding":false},{"id":233134,"name":"Hong Wang","orcid":"0000-0001-6258-4070","position":13,"is_corresponding":false},{"id":350578,"name":"Wen‐Zhe Ho","orcid":"0000-0002-5235-0606","position":14,"is_corresponding":false},{"id":510394,"name":"Ling Yang","orcid":"0000-0002-3105-3063","position":15,"is_corresponding":false},{"id":297243,"name":"Wenhui Hu","orcid":"0000-0001-8152-6116","position":16,"is_corresponding":false},{"id":299855,"name":"Yuanjun Zhu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:13:43.629667Z","pmid":"36793212","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":[]}