{"doi":"10.1101/2022.03.14.484360","title":"Cas9-Mediated Knockout of Ndrg2 Enhances the Regenerative Potential of Dendritic Cells for Wound Healing","abstract":"Abstract Chronic wounds impose a significant healthcare burden to a broad patient population. Cell based therapies, while having shown benefits for the treatment of chronic wounds, have not achieved widespread adoption into clinical practice. Here, we developed a novel CRISPR/Cas9 approach to precisely edit dendritic cells (DCs) to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing (scRNA-seq) of tolerogenic DCs, we discover N-myc downregulated gene 2 ( Ndrg2 ), which marks a specific population of DC progenitors, as a promising target for CRISPR knockout (KO). Ndrg2 -KO alters the transcriptomic profile of DCs and preserves an immature cell state with a strong, pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a hydrogel technology for in vivo cell delivery and developed a highly effective translational approach for DC based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in DCs for treating various types of chronic wounds.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301047,"datarank":0.1979646793857239,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.03317283608550744,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.03317283608550744,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991912,"name":"Dehua Zhao","orcid":"0000-0001-6303-4601","position":1,"is_corresponding":false},{"id":318647,"name":"Kellen Chen","orcid":"0000-0002-7023-7850","position":2,"is_corresponding":false},{"id":638345,"name":"Artem A. Trotsyuk","orcid":"0000-0001-8886-5583","position":3,"is_corresponding":false},{"id":318649,"name":"Clark A. Bonham","orcid":"0000-0002-7941-8607","position":4,"is_corresponding":false},{"id":852901,"name":"Katharina S. Fischer","orcid":"0000-0001-9759-6901","position":5,"is_corresponding":false},{"id":991913,"name":"Tim Kehl","orcid":"0000-0002-9523-7566","position":6,"is_corresponding":false},{"id":74452,"name":"Tobias Fehlmann","orcid":"0000-0003-1967-2918","position":7,"is_corresponding":false},{"id":318650,"name":"Dharshan Sivaraj","orcid":"0000-0001-7453-0045","position":8,"is_corresponding":false},{"id":638351,"name":"Autumn H. Greco","orcid":"0000-0002-7557-6800","position":9,"is_corresponding":false},{"id":644396,"name":"Sylvia E. Moortgat Illouz","orcid":"0000-0001-5302-598X","position":10,"is_corresponding":false},{"id":638347,"name":"Jagannath Padmanabhan","orcid":"0000-0003-1096-6637","position":11,"is_corresponding":false},{"id":638348,"name":"Janos A. Barrera","orcid":"0000-0001-6811-8337","position":12,"is_corresponding":false},{"id":658053,"name":"Ulrich Kneser","orcid":"0000-0002-3402-2860","position":13,"is_corresponding":false},{"id":991914,"name":"Hans‐Peter Lenhof","orcid":"0000-0002-5820-9961","position":14,"is_corresponding":false},{"id":1224,"name":"Michael Januszyk","orcid":"0000-0002-0313-0973","position":15,"is_corresponding":false},{"id":231540,"name":"Benjamin Lévi","orcid":"0000-0001-8272-7139","position":16,"is_corresponding":false},{"id":28480,"name":"Andreas Keller","orcid":"0000-0002-5361-0895","position":17,"is_corresponding":false},{"id":61819,"name":"Michael T. Longaker","orcid":"0000-0003-1430-8914","position":18,"is_corresponding":false},{"id":233741,"name":"Lei S. Qi","orcid":"0000-0002-3965-3223","position":19,"is_corresponding":false},{"id":1235,"name":"Geoffrey C. 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