{"doi":"10.1073/pnas.2525865123","title":"Identification of CD164 as an essential entry receptor for divergent adeno-associated viruses","abstract":"<jats:p>\n                    Recombinant adeno-associated viruses (rAAVs) are widely used for in vivo gene delivery. While KIAA0319L, known as AAV receptor (AAVR), is essential for the transduction of multiserotype AAVs, it is dispensable for AAV4-related (Clade G) AAVs. We conducted a genome-wide CRISPR/Cas9 screen and identified CD164, a type I transmembrane sialomucin, as an essential entry receptor for Clade G AAVs. Ablation of CD164 expression substantially impaired both entry and transduction of Clade G AAVs. CD164-targeting antibodies and soluble CD164 ectodomain effectively blocked transduction. AAV4 capsids colocalized with CD164 at the plasma membrane and in endosomal compartments. In vitro, CD164 interacted with AAV4 or AAVrh32.33 capsids at high affinity. Importantly, systemic administration of rAAV4 or rAAVrh32.33 in\n                    <jats:italic toggle=\"yes\">CD164</jats:italic>\n                    knockout (KO) mice resulted in nearly complete loss of transgene expression. These findings establish CD164 as an essential entry receptor for Clade G AAV vectors and uncover a distinct AAVR-independent mechanism of AAV tropism.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2026,"id":620549,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"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":1107308,"name":"Donovan Richart","orcid":"0000-0003-0048-4810","position":1,"is_corresponding":false},{"id":944476,"name":"Shane McFarlin","orcid":"0009-0002-1817-7915","position":2,"is_corresponding":false},{"id":406953,"name":"Fang Cheng","orcid":"0000-0002-2579-5220","position":3,"is_corresponding":false},{"id":1106979,"name":"Soo Yeun Park","orcid":"0000-0003-4821-2101","position":4,"is_corresponding":false},{"id":1602013,"name":"Anwen Zhang-Chen","orcid":null,"position":5,"is_corresponding":false},{"id":1266560,"name":"Richenda McFarlane","orcid":null,"position":6,"is_corresponding":false},{"id":228624,"name":"Chuan Xiao","orcid":"0000-0001-6599-8762","position":7,"is_corresponding":false},{"id":367144,"name":"Ziying Yan","orcid":"0000-0001-8210-5567","position":8,"is_corresponding":false},{"id":321300,"name":"Jianming Qiu","orcid":"0000-0001-9850-1695","position":9,"is_corresponding":false},{"id":706503,"name":"Xiujuan Zhang","orcid":"0009-0007-4268-4171","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of CD164 as an essential entry receptor for divergent adeno-associated viruses","abstract":"<jats:p>\n                    Recombinant adeno-associated viruses (rAAVs) are widely used for in vivo gene delivery. While KIAA0319L, known as AAV receptor (AAVR), is essential for the transduction of multiserotype AAVs, it is dispensable for AAV4-related (Clade G) AAVs. We conducted a genome-wide CRISPR/Cas9 screen and identified CD164, a type I transmembrane sialomucin, as an essential entry receptor for Clade G AAVs. Ablation of CD164 expression substantially impaired both entry and transduction of Clade G AAVs. CD164-targeting antibodies and soluble CD164 ectodomain effectively blocked transduction. AAV4 capsids colocalized with CD164 at the plasma membrane and in endosomal compartments. In vitro, CD164 interacted with AAV4 or AAVrh32.33 capsids at high affinity. Importantly, systemic administration of rAAV4 or rAAVrh32.33 in\n                    <jats:italic toggle=\"yes\">CD164</jats:italic>\n                    knockout (KO) mice resulted in nearly complete loss of transgene expression. These findings establish CD164 as an essential entry receptor for Clade G AAV vectors and uncover a distinct AAVR-independent mechanism of AAV tropism.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41785320","pmcid":"PMC12974471","openalex_id":"https://openalex.org/W7133905147","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"AI166293","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"AI180416","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"HL174593","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"AI182645","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"GM129525","title":null},{"funder_name":"Cystic Fibrosis Foundation","grant_id":"YAN23G0","title":null},{"funder_name":"Welch Foundation","grant_id":"AH-2126-20220331","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI182645","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM129525","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI150877","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL174593","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI180416","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI166293","title":null}],"total_grants":13,"fwci":20.9622,"citation_percentile":0.99431579,"influential_citations":0,"citation_trend":[{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.2525865123","host_type":"journal"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.2525865123","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2525865123","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2525865123","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41785320","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12974471/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12974471","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12974471?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Virus-based gene therapy research","CRISPR and Genetic Engineering","RNA Interference and Gene Delivery","Dependovirus","Animals","Humans","Mice","Virus Internalization","Genetic Vectors","Transduction, Genetic","Mice, Knockout","Receptors, Virus","Capsid","Receptors, Cell Surface","HEK293 Cells"],"mesh_terms":["Dependovirus","Animals","Capsid","Genetic Vectors","Humans","Receptors, Cell Surface","Receptors, Virus","Transduction, Genetic","Antigens, CD","Mice, Knockout","Mice","Virus Internalization","HEK293 Cells","CRISPR-Cas Systems"],"keywords":["Ectodomain","Transduction (biophysics)","Receptor","Transmembrane protein","Cricetulus","Signal transduction","Transgene","Endosome","In vivo","Transduction","Adeno-associated virus","Cd164"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"cellosaurus"},{"name":"refseq"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T11:24:47.446224Z","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":[]}