Molecular Therapy. Nucleic Acids最新文献

Breaking barriers: Aptamers in ocular disease treatment. 突破障碍：眼病治疗中的适配体。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-12-02 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102399

Tao Wang, Rakesh Naduvile Veedu

引用次数: 0

From classic to innovative: The continuation and modern application of calcium phosphate co-precipitation method in mRNA tumor delivery. 从经典到创新：磷酸钙共沉淀法在mRNA肿瘤传递中的延续与现代应用。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-29 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102384

Jiayu Zhang, Jun Chen

引用次数: 0

A dual functional mucus- and cell-penetrating peptide enhances mRNA lipid nanoparticle delivery to the lung. 双重功能的粘液和细胞穿透肽增强mRNA脂质纳米颗粒递送到肺。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-29 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102393

Sahana Kumar, Gregg A Duncan

引用次数: 0

A route to engineer a genome editor for gene therapy. 为基因治疗设计基因组编辑器的途径。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-29 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102394

Wenxia Yu, Yunbo Qiao

引用次数: 0

Cell-specific delivery of CRISPR-Cas9 with pseudotyped lentiviral particles: Just change the envelope. 用伪慢病毒颗粒对CRISPR-Cas9进行细胞特异性递送：只需改变包膜。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-27 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102395

Ángela Covo-Vergara, Laura Salaberry, Noelia Silva-Pilipich, Sandra Hervas-Stubbs, Cristian Smerdou

引用次数: 0

Double-stranded DNA invasion by anti-gene oligonucleotide clamps. 抗基因寡核苷酸夹的双链DNA入侵。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-23 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102385

Angana De, Raman Bahal

引用次数: 0

AAV-regulated Serpine2 overexpression promotes hair cell regeneration. aav调节Serpine2过表达促进毛细胞再生。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-17 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102396

Qiuhan Sun, Fangzhi Tan, Xinlin Wang, Xingliang Gu, Xin Chen, Yicheng Lu, Nianci Li, Xiaoyun Qian, Yinyi Zhou, Ziyu Zhang, Man Wang, Liyan Zhang, Busheng Tong, Jieyu Qi, Renjie Chai

{"title":"AAV-regulated Serpine2 overexpression promotes hair cell regeneration.","authors":"Qiuhan Sun, Fangzhi Tan, Xinlin Wang, Xingliang Gu, Xin Chen, Yicheng Lu, Nianci Li, Xiaoyun Qian, Yinyi Zhou, Ziyu Zhang, Man Wang, Liyan Zhang, Busheng Tong, Jieyu Qi, Renjie Chai","doi":"10.1016/j.omtn.2024.102396","DOIUrl":"10.1016/j.omtn.2024.102396","url":null,"abstract":"Inner ear hair cell (HC) damage is irreversible in mammals, but it has been shown that supporting cells (SCs) have the potential to differentiate into HCs. Serpine2, a serine protease inhibitor, encodes protease nexin 1, and this has been suggested to be a factor that promotes HC regeneration. In this study, we overexpressed Serpine2 in inner ear SCs cultured in two- and three-dimensional systems using the adeno-associated virus-inner ear (AAV-ie) vector, which promoted organoid expansion and HC differentiation. Overexpression of Serpine2 in the mouse cochlea through the round window membrane (RWM) injection promoted SC proliferation and HC regeneration, and the regenerated HCs were found to be derived from Lgr5+ SCs. Regenerated HCs have electrophysiological properties that are similar to those of native HCs. Notably, Serpine2 overexpression promoted HC survival and restored hearing of neomycin-damaged mice. In conclusion, our findings indicate that Serpine2 overexpression promotes HC regeneration and suggests that the utilization of inner ear progenitor cells in combination with AAVs might be a promising therapeutic target for hearing restoration.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"35 4","pages":"102396"},"PeriodicalIF":6.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA aptamers that modulate biological activity of model neurons. 调节模型神经元生物活性的DNA适体。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-16 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102392

Jenelle Rolli, Keenan Pearson, Brandon Wilbanks, Sybil C L Hrstka, Andrew P Minotti, Lorenz Studer, Arthur E Warrington, Nathan P Staff, L James Maher

{"title":"DNA aptamers that modulate biological activity of model neurons.","authors":"Jenelle Rolli, Keenan Pearson, Brandon Wilbanks, Sybil C L Hrstka, Andrew P Minotti, Lorenz Studer, Arthur E Warrington, Nathan P Staff, L James Maher","doi":"10.1016/j.omtn.2024.102392","DOIUrl":"10.1016/j.omtn.2024.102392","url":null,"abstract":"There is an urgent need for agents that promote health and regeneration of cells and tissues, specifically to treat diseases of the aging nervous system. Age-associated nervous system degeneration and various diseases are driven by many different biochemical stresses, often making it difficult to target any one disease cause. Our laboratory has previously identified DNA aptamers with apparent regenerative properties in murine models of multiple sclerosis by selecting aptamers that bind oligodendrocyte membrane preparations. Here, we selected from vast libraries of molecules (∼1014 unique DNAs) those with the ability to bind cultured human SH-SY5Y neuroblastoma cells as a neuronal model, followed by screening for aptamers capable of eliciting biological responses, with validation of binding in differentiated SH-SY5Y, human induced pluripotent stem cell (iPSC)-derived sensory neurons, and human embryonic stem cell (hESC)-derived cortical neurons. This demonstrates a proof-of-concept workflow to identify biologically active aptamers by cycles of cell selection.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"35 4","pages":"102392"},"PeriodicalIF":6.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer. 前列腺癌中CHD6启动子核小体的清除维持了内务转录程序。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-16 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102397

Lina Bu, Shaodong Huang, Ziyan Rao, Chenyang Wu, Bryan-Yu Sun, Yanhua Liu, Lin He, Dongyu Zhao

引用次数: 0

Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression. 通过结合crispr介导的内源性Gata4激活和外源性Mef2c和Tbx5表达直接心脏重编程。

IF 6.5 2区医学

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-15 eCollection Date: 2024-12-10 DOI: 10.1016/j.omtn.2024.102390

Peisen Huang, Jun Xu, Benjamin Keepers, Yifang Xie, David Near, Yangxi Xu, James Rock Hua, Brian Spurlock, Shea Ricketts, Jiandong Liu, Li Wang, Li Qian

{"title":"Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression.","authors":"Peisen Huang, Jun Xu, Benjamin Keepers, Yifang Xie, David Near, Yangxi Xu, James Rock Hua, Brian Spurlock, Shea Ricketts, Jiandong Liu, Li Wang, Li Qian","doi":"10.1016/j.omtn.2024.102390","DOIUrl":"10.1016/j.omtn.2024.102390","url":null,"abstract":"Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) can be achieved by ectopic expression of cardiac transcription factors (TFs) via viral vectors. However, risks like genomic mutations, viral toxicity, and immune response limited its clinical application. Transactivation of endogenous TFs emerges as an alternative approach that may partially mitigate some of the risks. In this study, we utilized a modified CRISPRa/dCas9 strategy to transactivate endogenous reprogramming factors MEF2C, GATA4, and TBX5 (MGT) to induce iCMs from both mouse and human fibroblasts. We identified single-guide RNAs (sgRNAs) targeting promoters and enhancers of the TFs capable of activating various degrees of endogenous gene expression. CRISPRa-mediated Gata4 activation, combined with exogenous expression of Mef2c and Tbx5, successfully converted fibroblasts into iCMs. Despite extensive sgRNA screening, transactivation of Mef2c and Tbx5 via CRISPRa remained less effective, potentially due to de novo epigenetic barriers. While future work and refined technologies are needed to determine whether cardiac reprogramming could be achieved solely through CRISPRa activation of endogenous factors, our findings provide proof of concept that reliance on exogenous TFs for reprogramming can be reduced through CRISPRa-mediated activation of endogenous factors, particularly Gata4, offering a novel strategy to convert scar-forming fibroblasts into iCMs for regenerative purposes.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"35 4","pages":"102390"},"PeriodicalIF":6.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0