DNA and cell biology reports最新文献

{"title":"Correction of Disease Phenotype in Pompe Disease Knockout Mice Following Cationic Lipid-GL-67-Mediated Gene Therapy.","authors":"Frank Martiniuk, Justin Martiniuk, Adra Mack, Seng H Cheng","doi":"10.1089/dcbr.2025.0025","DOIUrl":"10.1089/dcbr.2025.0025","url":null,"abstract":"<p><strong>Background: </strong>Genetic deficiency of lysosomal acid α-glucosidase or acid maltase (GAA) results in Pompe disease (PD) or glycogen storage disease type II, encompassing subtypes of varying severity. The infantile form presents as hypotonia, muscle weakness, and congestive heart failure in the first year, while the adult onset forms are limited to skeletal muscle. Gene therapy for diseases that affect muscles or organs (as PD) may be very difficult due to their size or location and our ability to transfect these organs with high efficiency.</p><p><strong>Methods: </strong>We evaluated a plasmid vector carrying the cytomegalovirus promoter linked to the human <i>GAA</i> cDNA complexed with the cationic lipid GL-67 as a delivery system for therapy of PD.</p><p><strong>Results: </strong>A human PD fibroblast cell line was transiently transfected with increasing amounts of the cationic lipid GL-67 complexed to the human <i>GAA</i> expression plasmid. Cells showed a significant increase in human GAA activity with 20 nmol of the cationic lipid, resulting in maximal expression. GAA knockout mice were treated intraperitoneally every 2 weeks for four months with 100 µg of plasmid and 2 mM GL-67 lipid. Tissues, including heart, diaphragm, and skeletal muscle showed substantial increase in GAA activity. More important, the clinical phenotype of hind and forelimb muscle weakness was reversed and life span extended to almost normal longevity.</p><p><strong>Conclusions: </strong>These data suggest that cationic lipid mediated gene delivery of the human <i>GAA</i> cDNA may be an effective treatment for PD.</p>","PeriodicalId":521053,"journal":{"name":"DNA and cell biology reports","volume":"6 1","pages":"64-75"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA Sequencing Identifies CCR6-Driven Immune Landscape Changes in RM1 Prostate Cancer Bone Metastasis.","authors":"Marxa L Figueiredo","doi":"10.1089/dcbr.2025.0001","DOIUrl":"10.1089/dcbr.2025.0001","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer commonly metastasizes to bone, creating an immunosuppressive microenvironment that supports tumor progression. The RM1 (Ras/Myc) mouse model is a valuable tool for studying interactions between prostate tumors and the bone marrow immune landscape.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed to investigate how CCR6 deficiency affects immune cell comsmunication in bone marrow from RM1 prostate cancer bone metastasis. Immune responses were compared between wild-type and CCR6 knockout (CCR6ko) C57BL/6-mice injected with RM1-BoM3 cells.</p><p><strong>Results: </strong>Distinct immune cell dynamics were observed between the two groups. CCR6ko bone marrow showed enhanced signaling from macrophages, regulatory T cells, and myeloid-derived suppressor cell-like cells, with altered receptor activity in naïve T cells, NK cells, and conventional dendritic cells. Differential gene expression highlighted immune regulation pathways and transcriptional networks centered on JUN, JUNB, and FOSB, linked to immune suppression and tumor progression. Cell-cell communication analysis revealed changes in CCL, TGFb, MIF, and CXCL pathways, aligning with observations in human castration-resistant prostate cancer (CRPC) bone-metastasis. Profiling of immune cell populations showed increased tumor-infiltrating monocytic cells, M2 macrophages, and NKT-like CD8 cells in RM1 tumors compared to CCR6ko bone marrow. Pathway enrichment analysis identified upregulated pathways, including IL-17 signaling and osteoclast differentiation, associated with immune-modulation and inflammation. Gene regulatory networks in the RM1 bone metastasis microenvironment involved NFKB1, STAT1, IRF8, and JUN family proteins, emphasizing their roles in immune suppression and tumor progression.</p><p><strong>Conclusions: </strong>These results suggest that targeting CCR6 may enhance immunotherapy efficacy in prostate cancer bone metastasis by reshaping the immune microenvironment. Validation in human CRPC bone metastasis datasets revealed conserved immune interactions.</p>","PeriodicalId":521053,"journal":{"name":"DNA and cell biology reports","volume":"6 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}