Pub Date : 2024-08-21DOI: 10.1016/j.omtn.2024.102293
Walison Nunes da Silva, Pedro Henrique Dias Moura Prazeres, Pedro Pires Goulart Guimarães
{"title":"PLA-PEG as an alternative to PEGylated lipids for nanoparticle-based DNA vaccination against SARS-CoV-2","authors":"Walison Nunes da Silva, Pedro Henrique Dias Moura Prazeres, Pedro Pires Goulart Guimarães","doi":"10.1016/j.omtn.2024.102293","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102293","url":null,"abstract":"","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"60 1","pages":"102293"},"PeriodicalIF":8.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The use of mRNA and ribonucleoproteins (RNPs) as therapeutic agents is a promising strategy for treating diseases such as cancer and infectious diseases. This review provides recent advancements and challenges in mRNA- and RNP-based therapies, focusing on delivery systems such as lipid nanoparticles (LNPs), which ensure efficient delivery to target cells. Strategies such as microfluidic devices are employed to prepare LNPs loaded with mRNA and RNPs, demonstrating effective genome editing and protein expression and . These applications extend to cancer treatment and infectious disease management, with promising results in genome editing for cancer therapy using LNPs encapsulating Cas9 mRNA and single-guide RNA. In addition, tissue-specific targeting strategies offer potential for improved therapeutic outcomes and reduced off-target effects. Despite progress, challenges such as optimizing delivery efficiency and targeting remain. Future research should enhance delivery efficiency, explore tissue-specific targeting, investigate combination therapies, and advance clinical translation. In conclusion, mRNA- and RNP-based therapies offer a promising avenue for treating various diseases and have the potential to revolutionize medicine, providing new hope for patients worldwide.
{"title":"Advancements and challenges in mRNA and ribonucleoprotein-based therapies: From delivery systems to clinical applications","authors":"Zohre Eftekhari, Horieh Zohrabi, Akbar Oghalaie, Tahereh Ebrahimi, Fatemeh Sadat Shariati, Mahdi Behdani, Fatemeh Kazemi-Lomedasht","doi":"10.1016/j.omtn.2024.102313","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102313","url":null,"abstract":"The use of mRNA and ribonucleoproteins (RNPs) as therapeutic agents is a promising strategy for treating diseases such as cancer and infectious diseases. This review provides recent advancements and challenges in mRNA- and RNP-based therapies, focusing on delivery systems such as lipid nanoparticles (LNPs), which ensure efficient delivery to target cells. Strategies such as microfluidic devices are employed to prepare LNPs loaded with mRNA and RNPs, demonstrating effective genome editing and protein expression and . These applications extend to cancer treatment and infectious disease management, with promising results in genome editing for cancer therapy using LNPs encapsulating Cas9 mRNA and single-guide RNA. In addition, tissue-specific targeting strategies offer potential for improved therapeutic outcomes and reduced off-target effects. Despite progress, challenges such as optimizing delivery efficiency and targeting remain. Future research should enhance delivery efficiency, explore tissue-specific targeting, investigate combination therapies, and advance clinical translation. In conclusion, mRNA- and RNP-based therapies offer a promising avenue for treating various diseases and have the potential to revolutionize medicine, providing new hope for patients worldwide.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"41 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.1016/j.omtn.2024.102311
Akiko Doi, Conor Delaney, David Tanner, Kirk Burkhart, Robert D. Bell
RNA exon editing is a therapeutic strategy for correcting disease-causing mutations by inducing -splicing between a synthetic RNA molecule and an endogenous pre-mRNA target, resulting in functionally restored mRNA and protein. This approach enables the replacement of exons at the kilobase scale, addresses multiple mutations with a single therapy, and maintains native gene expression without changes to DNA. For genes larger than 5 kb, RNA exon editors can be delivered in a single vector despite AAV capacity limitations because only mutated exons need to be replaced. While correcting mutations by -splicing has been previously demonstrated, prior attempts were hampered by low efficiency or lack of translation in preclinical models. Advances in synthetic biology, next-generation sequencing, and bioinformatics, with a deeper understanding of mechanisms controlling RNA splicing, have triggered a re-emergence of -splicing and the development of new RNA exon editing molecules for treating human disease, including the first application in a clinical trial (this study was registered at []). Here, we provide an overview of RNA splicing, the history of -splicing, previously reported therapeutic applications, and how modern advances are enabling the discovery of RNA exon editing molecules for genetic targets unable to be addressed by conventional gene therapy and gene editing approaches.
{"title":"RNA exon editing: Splicing the way to treat human diseases","authors":"Akiko Doi, Conor Delaney, David Tanner, Kirk Burkhart, Robert D. Bell","doi":"10.1016/j.omtn.2024.102311","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102311","url":null,"abstract":"RNA exon editing is a therapeutic strategy for correcting disease-causing mutations by inducing -splicing between a synthetic RNA molecule and an endogenous pre-mRNA target, resulting in functionally restored mRNA and protein. This approach enables the replacement of exons at the kilobase scale, addresses multiple mutations with a single therapy, and maintains native gene expression without changes to DNA. For genes larger than 5 kb, RNA exon editors can be delivered in a single vector despite AAV capacity limitations because only mutated exons need to be replaced. While correcting mutations by -splicing has been previously demonstrated, prior attempts were hampered by low efficiency or lack of translation in preclinical models. Advances in synthetic biology, next-generation sequencing, and bioinformatics, with a deeper understanding of mechanisms controlling RNA splicing, have triggered a re-emergence of -splicing and the development of new RNA exon editing molecules for treating human disease, including the first application in a clinical trial (this study was registered at []). Here, we provide an overview of RNA splicing, the history of -splicing, previously reported therapeutic applications, and how modern advances are enabling the discovery of RNA exon editing molecules for genetic targets unable to be addressed by conventional gene therapy and gene editing approaches.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"9 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1016/j.omtn.2024.102307
Irena Bočkaj, Anna Moreno Garcia, Pablo de Miguel Herraiz, Sonay Keskin, Vanessa Zancanella, Şeyda Acar Broekmans, Astrid Vallès, Ying Poi Liu, Melvin Evers, Morgane Wartel
Given that numerous genetic disorders, driven by diverse pathogenic mechanisms, may be amenable to recombinant adeno-associated virus (rAAV)-delivered gene therapies, the sustained innovation of rAAV-based therapeutic modalities is crucial. The progression and severity of genetic diseases can be reduced by targeting the toxic transcripts of a defective gene using microRNA (miRNA)-based miQURE technology delivered within an AAV vector. By adapting the delivered cassette, it may be possible to simultaneously regulate the expression profile of multiple genes involved in the pathogenesis of complex genetic diseases. The established miQURE gene silencing strategy was expanded by concatenating several miQURE molecules in a single construct, resulting in the novel linQURE platform. Here, a proof of mechanism is established by demonstrating that linQURE technology enables the concomitant expression of two synthetic miRNAs and , allowing more efficient downregulation of their disease-causing mRNA targets. This approach supports the development of multi-targeting therapeutic strategies, enabling gene therapy products to adapt to more complex multigenic indications, thus expanding the toolbox of readily available gene therapies.
{"title":"LinQURE: A novel AAV gene silencing platform that supports multi-transcript targeting for complex disorders","authors":"Irena Bočkaj, Anna Moreno Garcia, Pablo de Miguel Herraiz, Sonay Keskin, Vanessa Zancanella, Şeyda Acar Broekmans, Astrid Vallès, Ying Poi Liu, Melvin Evers, Morgane Wartel","doi":"10.1016/j.omtn.2024.102307","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102307","url":null,"abstract":"Given that numerous genetic disorders, driven by diverse pathogenic mechanisms, may be amenable to recombinant adeno-associated virus (rAAV)-delivered gene therapies, the sustained innovation of rAAV-based therapeutic modalities is crucial. The progression and severity of genetic diseases can be reduced by targeting the toxic transcripts of a defective gene using microRNA (miRNA)-based miQURE technology delivered within an AAV vector. By adapting the delivered cassette, it may be possible to simultaneously regulate the expression profile of multiple genes involved in the pathogenesis of complex genetic diseases. The established miQURE gene silencing strategy was expanded by concatenating several miQURE molecules in a single construct, resulting in the novel linQURE platform. Here, a proof of mechanism is established by demonstrating that linQURE technology enables the concomitant expression of two synthetic miRNAs and , allowing more efficient downregulation of their disease-causing mRNA targets. This approach supports the development of multi-targeting therapeutic strategies, enabling gene therapy products to adapt to more complex multigenic indications, thus expanding the toolbox of readily available gene therapies.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"99 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1016/j.omtn.2024.102310
Somayeh Handali, Mohsen Rezaei
Viral infections are one of the leading causes of death in the world. One main challenge in fighting against these diseases is the unavailability of effective eradicating drugs and specific treatments. Nanocarriers and aptamer-decorated nanocarriers are designed to attach to many targets, including viral particles. By lowering the viral infectivity and attachment capability, they add therapeutic values even without containing antiviral drugs. Nevertheless, the nanoparticles (NPs) with encapsulated antiviral drugs can display extra therapeutic effects. Furthermore, it has been shown that aptamers can bind to viral particles and nanocarriers, presenting promising approaches for the identification of viruses and treatment of viral infections. Although there is no satisfying literature revealing the strong therapeutic potential of nanotechnology against COVID-19, the following information can provide new perspectives for upcoming investigations pertaining to developing effective aptamer-nanocarrier agents against COVID-19.
{"title":"Aptamer-decorated nanocarriers for viral adsorption: A special look at COVID-19","authors":"Somayeh Handali, Mohsen Rezaei","doi":"10.1016/j.omtn.2024.102310","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102310","url":null,"abstract":"Viral infections are one of the leading causes of death in the world. One main challenge in fighting against these diseases is the unavailability of effective eradicating drugs and specific treatments. Nanocarriers and aptamer-decorated nanocarriers are designed to attach to many targets, including viral particles. By lowering the viral infectivity and attachment capability, they add therapeutic values even without containing antiviral drugs. Nevertheless, the nanoparticles (NPs) with encapsulated antiviral drugs can display extra therapeutic effects. Furthermore, it has been shown that aptamers can bind to viral particles and nanocarriers, presenting promising approaches for the identification of viruses and treatment of viral infections. Although there is no satisfying literature revealing the strong therapeutic potential of nanotechnology against COVID-19, the following information can provide new perspectives for upcoming investigations pertaining to developing effective aptamer-nanocarrier agents against COVID-19.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"1 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mature microRNAs (miRNAs) are short, single-stranded RNAs that bind to target mRNAs and induce translational repression and gene silencing. Many miRNAs discovered in animals have been implicated in diseases and have recently been pursued as therapeutic targets. However, conventional pharmacological screening for candidate small-molecule drugs can be time-consuming and labor-intensive. Therefore, developing a computational program to assist mature miRNA-targeted drug discovery is desirable. Our previous work () revealed that the unique functional loops formed during Argonaute-mediated miRNA-mRNA interactions have stable structural characteristics and may serve as potential targets for small-molecule drug discovery. Developing drugs specifically targeting disease-related mature miRNAs and their target mRNAs would avoid affecting unrelated ones. Here, we present SMTRI, a convolutional neural network-based approach for efficiently predicting small molecules that target RNA secondary structural motifs formed by interactions between miRNAs and their target mRNAs. Measured on three additional testing sets, SMTRI outperformed state-of-the-art algorithms by 12.9%–30.3% in AUC and 2.0%–18.4% in accuracy. Moreover, four case studies on the published experimentally validated RNA-targeted small molecules also revealed the reliability of SMTRI.
{"title":"SMTRI: A deep learning-based web service for predicting small molecules that target miRNA-mRNA interactions","authors":"Huan Xiao, Yihao Zhang, Xin Yang, Sifan Yu, Ziqi Chen, Aiping Lu, Zongkang Zhang, Ge Zhang, Bao-Ting Zhang","doi":"10.1016/j.omtn.2024.102303","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102303","url":null,"abstract":"Mature microRNAs (miRNAs) are short, single-stranded RNAs that bind to target mRNAs and induce translational repression and gene silencing. Many miRNAs discovered in animals have been implicated in diseases and have recently been pursued as therapeutic targets. However, conventional pharmacological screening for candidate small-molecule drugs can be time-consuming and labor-intensive. Therefore, developing a computational program to assist mature miRNA-targeted drug discovery is desirable. Our previous work () revealed that the unique functional loops formed during Argonaute-mediated miRNA-mRNA interactions have stable structural characteristics and may serve as potential targets for small-molecule drug discovery. Developing drugs specifically targeting disease-related mature miRNAs and their target mRNAs would avoid affecting unrelated ones. Here, we present SMTRI, a convolutional neural network-based approach for efficiently predicting small molecules that target RNA secondary structural motifs formed by interactions between miRNAs and their target mRNAs. Measured on three additional testing sets, SMTRI outperformed state-of-the-art algorithms by 12.9%–30.3% in AUC and 2.0%–18.4% in accuracy. Moreover, four case studies on the published experimentally validated RNA-targeted small molecules also revealed the reliability of SMTRI.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"73 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient. In this study, we identified two subgroups with distinct senescent clusters among geriatric breast cancer patients through multi-omics analysis. Using various machine learning algorithms, we developed a comprehensive scoring model called “Sene_Signature,” which more accurately distinguished elderly breast cancer patients compared with existing methods and better predicted their prognosis. The Sene_Signature was correlated with tumor immune cell infiltration, as supported by single-cell transcriptomics, RNA sequencing, and pathological data. Furthermore, we observed increased drug responsiveness in patients with a high Sene_Signature to treatments targeting the epidermal growth factor receptor and cell-cycle pathways. We also established a user-friendly web platform to assist investigators in assessing Sene_Signature scores and predicting treatment responses for elderly breast cancer patients. In conclusion, we developed a novel model for evaluating prognosis and therapeutic responses, providing a potential molecular classification that assists in the pre-treatment assessment of geriatric breast cancer.
{"title":"Molecular classification of geriatric breast cancer displays distinct senescent subgroups of prognostic significance","authors":"Xia Wu, Mengxin Chen, Kang Liu, Yixin Wu, Yun Feng, Shiting Fu, Huaimeng Xu, Yongqi Zhao, Feilong Lin, Liang Lin, Shihui Ye, Junqiang Lin, Taiping Xiao, Wenhao Li, Meng Lou, Hongyu Lv, Ye Qiu, Ruifan Yu, Wenyan Chen, Mengyuan Li, Xu Feng, Zhongbing Luo, Lu Guo, Hao Ke, Limin Zhao","doi":"10.1016/j.omtn.2024.102309","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102309","url":null,"abstract":"Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient. In this study, we identified two subgroups with distinct senescent clusters among geriatric breast cancer patients through multi-omics analysis. Using various machine learning algorithms, we developed a comprehensive scoring model called “Sene_Signature,” which more accurately distinguished elderly breast cancer patients compared with existing methods and better predicted their prognosis. The Sene_Signature was correlated with tumor immune cell infiltration, as supported by single-cell transcriptomics, RNA sequencing, and pathological data. Furthermore, we observed increased drug responsiveness in patients with a high Sene_Signature to treatments targeting the epidermal growth factor receptor and cell-cycle pathways. We also established a user-friendly web platform to assist investigators in assessing Sene_Signature scores and predicting treatment responses for elderly breast cancer patients. In conclusion, we developed a novel model for evaluating prognosis and therapeutic responses, providing a potential molecular classification that assists in the pre-treatment assessment of geriatric breast cancer.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"43 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1016/j.omtn.2024.102306
Merve Keles, Steve Grein, Natali Froese, Dagmar Wirth, Felix A. Trogisch, Rhys Wardman, Shruthi Hemanna, Nina Weinzierl, Philipp-Sebastian Koch, Stefanie Uhlig, Santosh Lomada, Gesine M. Dittrich, Malgorzata Szaroszyk, Ricarda Haustein, Jan Hegermann, Abel Martin-Garrido, Johann Bauersachs, Derk Frank, Norbert Frey, Karen Bieback, Julio Cordero, Gergana Dobreva, Thomas Wieland, Joerg Heineke
Pathological cardiac remodeling predisposes individuals to developing heart failure. Here, we investigated two co-regulated long non-coding RNAs (lncRNAs), termed and , which are upregulated in failing hearts of patients and mice. Cardiac overexpression of and aggravated myocardial dysfunction and enhanced hypertrophic and fibrotic remodeling in mice exposed to pressure overload. Compound knockout (KO) mice showed markedly reduced myocardial hypertrophy, fibrosis, and dysfunction, while exhibiting increased angiogenesis during short and prolonged periods of pressure overload. Paradoxically, KO mice suffered from sudden death during prolonged overload, possibly due to cardiac arrhythmia. and , which are mainly expressed in endothelial cells (ECs) in the heart, where they inhibit pro-angiogenic gene expression, are strongly secreted within extracellular vesicles (EVs). These EVs transfer lncRNAs to cardiomyocytes, where they bind and activate calmodulin-dependent kinase II, and impact pro-hypertrophic gene expression and calcium homeostasis. Therefore, we reveal a crucial lncRNA-based mechanism of EC-cardiomyocyte crosstalk during heart failure, which could be specifically modified in the future for therapeutic purposes.
{"title":"Endothelial derived, secreted long non-coding RNAs Gadlor1 and Gadlor2 aggravate cardiac remodeling","authors":"Merve Keles, Steve Grein, Natali Froese, Dagmar Wirth, Felix A. Trogisch, Rhys Wardman, Shruthi Hemanna, Nina Weinzierl, Philipp-Sebastian Koch, Stefanie Uhlig, Santosh Lomada, Gesine M. Dittrich, Malgorzata Szaroszyk, Ricarda Haustein, Jan Hegermann, Abel Martin-Garrido, Johann Bauersachs, Derk Frank, Norbert Frey, Karen Bieback, Julio Cordero, Gergana Dobreva, Thomas Wieland, Joerg Heineke","doi":"10.1016/j.omtn.2024.102306","DOIUrl":"https://doi.org/10.1016/j.omtn.2024.102306","url":null,"abstract":"Pathological cardiac remodeling predisposes individuals to developing heart failure. Here, we investigated two co-regulated long non-coding RNAs (lncRNAs), termed and , which are upregulated in failing hearts of patients and mice. Cardiac overexpression of and aggravated myocardial dysfunction and enhanced hypertrophic and fibrotic remodeling in mice exposed to pressure overload. Compound knockout (KO) mice showed markedly reduced myocardial hypertrophy, fibrosis, and dysfunction, while exhibiting increased angiogenesis during short and prolonged periods of pressure overload. Paradoxically, KO mice suffered from sudden death during prolonged overload, possibly due to cardiac arrhythmia. and , which are mainly expressed in endothelial cells (ECs) in the heart, where they inhibit pro-angiogenic gene expression, are strongly secreted within extracellular vesicles (EVs). These EVs transfer lncRNAs to cardiomyocytes, where they bind and activate calmodulin-dependent kinase II, and impact pro-hypertrophic gene expression and calcium homeostasis. Therefore, we reveal a crucial lncRNA-based mechanism of EC-cardiomyocyte crosstalk during heart failure, which could be specifically modified in the future for therapeutic purposes.","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"6 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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