{"doi":"10.1016/j.ymthe.2006.05.015","title":"Optimization and Functional Effects of Stable Short Hairpin RNA Expression in Primary Human Lymphocytes via Lentiviral Vectors","abstract":null,"journal":"Molecular Therapy","year":2006,"id":628721,"datarank":0.7555428903620446,"base_score":5.0369526024136295,"endowment":5.0369526024136295,"self_citation_contribution":0.7555428903620446,"citation_network_contribution":0.0,"self_endowment_contribution":0.7555428903620446,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":153,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1627946,"name":"F. Xiao-Feng Qin","orcid":null,"position":1,"is_corresponding":false},{"id":557414,"name":"Vincent C. Auyeung","orcid":"0000-0001-6273-1595","position":2,"is_corresponding":false},{"id":1627948,"name":"Si Hua Mao","orcid":null,"position":3,"is_corresponding":false},{"id":1627950,"name":"Sam K.P. Kung","orcid":null,"position":4,"is_corresponding":false},{"id":6310,"name":"David Baltimore","orcid":"0000-0001-8723-8190","position":5,"is_corresponding":false},{"id":1627951,"name":"Irvin S.Y. Chen","orcid":null,"position":6,"is_corresponding":false},{"id":585617,"name":"Dong Sung An","orcid":"0000-0002-7020-9470","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Optimization and Functional Effects of Stable Short Hairpin RNA Expression in Primary Human Lymphocytes via Lentiviral Vectors","abstract":"Specific, potent, and sustained short hairpin RNA (shRNA)-mediated gene silencing is crucial for the successful application of RNA interference technology to therapeutic interventions. We examined the effects of shRNA expression in primary human lymphocytes (PBLs) using lentiviral vectors bearing different RNA polymerase III promoters. We found that the U6 promoter is more efficient than the H1 promoter for shRNA expression and for reducing expression of CCR5 in PBLs. However, shRNA expression from the U6 promoter resulted in a gradual decline of the transduced cell populations. With one CCR5 shRNA this decline could be attributed to elevated apoptosis but another CCR5 shRNA that caused cytotoxicity did not show evidence of apoptosis, suggesting sequence-specific mechanisms for cytotoxicity. In contrast to the U6 promoter, PBLs transduced by vectors expressing shRNAs from the H1 promoter could be maintained without major cytotoxic effects. Since a lower level of shRNA expression appears to be advantageous to maintaining the shRNA-transduced population, lentiviral vectors bearing the H1 promoter are more suitable for stable transduction and expression of shRNA in primary human T lymphocytes. Our results suggest that functional shRNA screens should include tests for both potency and adverse metabolic effects upon primary cells.","is_dataset_classified":null,"base_score":5.0369526024136295,"endowment":5.0369526024136295,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16844419","pmcid":"PMC2562632","openalex_id":"https://openalex.org/W2125881252","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI 28697","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI100652","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI039975","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI028697","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI042549","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI 39975-05","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL086409","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI 42549-04","title":null}],"total_grants":8,"fwci":5.8508,"citation_percentile":0.97127659,"influential_citations":0,"citation_trend":[{"year":2012,"count":11},{"year":2013,"count":16},{"year":2014,"count":11},{"year":2015,"count":7},{"year":2016,"count":7},{"year":2017,"count":5},{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":4},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.sciencedirect.com/science/article/pii/S1525001606002139/pdf","host_type":"journal"},{"url":"https://www.sciencedirect.com/science/article/pii/S1525001606002139/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1525001606002139?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1525001606002139?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ymthe.2006.05.015","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16844419","host_type":"repository"},{"url":"https://authors.library.caltech.edu/102627/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2562632","host_type":"repository"}],"fields_of_study":["RNA Interference and Gene Delivery","Virus-based gene therapy research","RNA Research and Splicing","Animals","Apoptosis","Cells, Cultured","Gene Dosage","Gene Expression","Genetic Vectors","Humans","Interferons","Lentivirus","Lymphocytes","Mice","Models, Biological","Nucleic Acid Conformation","Promoter Regions, Genetic","RNA Interference","Receptors, CCR5"],"mesh_terms":["Animals","Cells, Cultured","Genetic Vectors","Humans","Interferons","Lymphocytes","Models, Biological","Nucleic Acid Conformation","Promoter Regions, Genetic","Gene Expression","Lentivirus","Apoptosis","Gene Dosage","Receptors, CCR5","RNA Interference","Mice"],"keywords":["Small hairpin RNA","RNA interference","Gene silencing","Biology","Molecular biology","Transduction (biophysics)","Viral vector","RNA polymerase III","Gene expression","RNA","Promoter","Cell biology","Gene knockdown","Apoptosis","Gene","Recombinant DNA","RNA polymerase","Genetics","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T14:46:45.086866Z","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":[]}