Molecular Therapy最新文献_第9页

Gene Therapy for Hemophilia - From Basic Science to First Approvals of "One-and-Done" Therapies.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.043

Roland W Herzog, Radoslaw Kaczmarek, Katherine A High

{"title":"Gene Therapy for Hemophilia - From Basic Science to First Approvals of \"One-and-Done\" Therapies.","authors":"Roland W Herzog, Radoslaw Kaczmarek, Katherine A High","doi":"10.1016/j.ymthe.2025.03.043","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.043","url":null,"abstract":"Realistic paths to gene therapy for the X-linked bleeding disorder hemophilia started to materialize in the mid 1990s, resulting in disease correction in small and large animal models. Out of a diversity of approaches, in vivo adeno-associated viral (AAV) gene transfer to hepatocytes emerged as the most promising strategy, eventually forming the basis for multiple advanced clinical trials and regulatory approval of two products for the treatment of hemophilia B (coagulation factor IX deficiency) and one for hemophilia A (factor VIII deficiency). Ideally, gene therapy is effective with a single administration, thus providing therapeutic factor levels over a period of years, without the need for frequent injections. Overcoming multiple obstacles, some not predicted by pre-clinical studies, sustained partial to complete correction of coagulation for several years to an entire decade has now been documented in patients, with observation ongoing. A hyperactive form of FIX improved efficacy in hemophilia B, and superior engineered variants of FVIII are emerging. Nonetheless, challenges remain, including pre-existing immunity to AAV capsids, toxicities, inter-patient variability in response to treatment, and difficulty in obtaining durable therapeutic expression of FVIII. In alternative approaches, in vivo gene editing and ex vivo gene therapies targeting hemopoietic cells are in development.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An engineered antibody-lectin conjugate targeting the HIV glycan shield protects humanized mice against HIV challenge.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.039

Rashmi Kumariya, Jiadong Sun, Sabrina Lusvarghi, Sijy O'Dell, Gengxiang Zhao, Nicole A Doria-Rose, Carole A Bewley

{"title":"An engineered antibody-lectin conjugate targeting the HIV glycan shield protects humanized mice against HIV challenge.","authors":"Rashmi Kumariya, Jiadong Sun, Sabrina Lusvarghi, Sijy O'Dell, Gengxiang Zhao, Nicole A Doria-Rose, Carole A Bewley","doi":"10.1016/j.ymthe.2025.03.039","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.039","url":null,"abstract":"Enveloped viruses responsible for global health pandemics often display a glycan shield on their surface envelope glycoproteins. In HIV, the glycan shield is formed by clusters of high-mannose glycans and plays essential roles in viral fitness and immune evasion. A few mannose-binding lectins potently inactivate HIV but have not been fully exploited due to poor pharmacokinetics and short serum half-lives. To address this, we engineered an antibody-lectin conjugate comprising the anti-HIV lectin griffithsin (GRFT) to the Fc region of human IgG1, with the aim of extending its serum half-life and augmenting anti-HIV activity by inducing immune effector responses. Engineered mGRFT-Fc produced in bacteria exhibited picomolar anti-HIV activity and an extended serum half-life, and mGRFT-Fc produced in mammalian cells (mGRFT-Fcglyc) elicited immune effector responses. In HIV-infected CD34+-humanized mice, both GRFT and mGRFT-Fcglyc effectively suppressed viral loads for up to 8 weeks after a single dose. Significantly, mGRFT-Fcglyc prevented HIV infection by neutralizing HIV and provided sustained protection from break through infections via Fc-mediated immune effector responses, exhibiting a dual mode of protection. This study demonstrates the successful engineering of a lectin-based biologic and provides early evidence that a glycan-targeting agent alone can confer protection from viral infection in vivo.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The deLIVERed promises of gene therapy: past, present and future of liver-directed gene therapy.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.041

Francesco Puzzo, Mark A Kay

{"title":"The deLIVERed promises of gene therapy: past, present and future of liver-directed gene therapy.","authors":"Francesco Puzzo, Mark A Kay","doi":"10.1016/j.ymthe.2025.03.041","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.041","url":null,"abstract":"Gene therapy has revolutionized modern medicine by offering innovative treatments for genetic and acquired diseases. The liver, has and continues as a prime target for in vivo gene therapy due to its essential biological functions, vascular access to the major target cell (hepatocytes) and relatively immunotolerant environment. Adeno-associated virus (AAV) vectors have become the cornerstone of liver-directed therapies, demonstrating remarkable success in conditions such as hemophilia A and B, with FDA approved therapies like Etranacogene Dezaparvovec, Beqvez, and Roctavian marking milestones in the field. Despite these advances, challenges persist, including vector immunogenicity, species-specific barriers, and high manufacturing costs. Innovative strategies, such as capsid engineering, immune modulation, and novel delivery systems are continuing to address these issues in expanding the scope of therapeutic applications. Some of the challenges with many new therapies result in the discordance between preclinical success and translation into humans. The advent of various genome-editing tools to repair genomic mutations or insert therapeutic DNAs into precise locations in the genome further enhances the potential for a single-dose medicine that will offer durable life-long therapeutic treatments. As advancements accelerate, liver-targeted gene therapy is poised to continue to transform the treatment landscape for both genetic and acquired disorders, for which unmet challenges remain.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immuno-oncology recapitulates ontogeny: Modern cell and gene therapy for cancer.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.042

Neil Carleton, Aaron B I Rosen, Jishnu Das, Michael T Lotze

{"title":"Immuno-oncology recapitulates ontogeny: Modern cell and gene therapy for cancer.","authors":"Neil Carleton, Aaron B I Rosen, Jishnu Das, Michael T Lotze","doi":"10.1016/j.ymthe.2025.03.042","DOIUrl":"10.1016/j.ymthe.2025.03.042","url":null,"abstract":"Immuno-oncology (IO) has had over a century to develop from the original seminal insights of Virchow in 1863, seeing inflammation and lymphoid infiltrates as a common anlage for many adult tumors. That IO has become a central pillar of cancer treatment has come about because of the remarkable clinical and subsequent commercial success of immune checkpoint blockade (ICB) in the last fifteen years. This as well includes now approved cell and gene therapies for patients with cancer including an armed adenovirus, oncolytic herpes virus, and adoptive transfer of dendritic cells, chimeric antigen receptor T cells (CAR-T), and tumor infiltrating lymphocytes (TILs). The evolution of such applications required the stepwise development of a deeper understanding of the molecular biology of cancer and the physiology of immunobiology. This also recapitulates, in a broader sense, our evolutionary trajectory with capture of 'evolvability', not only across the development of species, but also within individuals. This review covers how our foundational understanding of immune system learning and evolvability have facilitated better understanding of the co-evolutionary interactions between the epithelium and immune system. We highlight examples of this in breast, colon, prostate, pancreas, and lung cancer, and provide examples of next-generation cell and gene therapies that intercept cancer development.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The curious case of AAV immunology.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.037

Allison M Keeler, Wei Zhan, Sanjay Ram, Katherine A Fitzgerald, Guangping Gao

{"title":"The curious case of AAV immunology.","authors":"Allison M Keeler, Wei Zhan, Sanjay Ram, Katherine A Fitzgerald, Guangping Gao","doi":"10.1016/j.ymthe.2025.03.037","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.037","url":null,"abstract":"Immune responses to adeno-associated virus (AAV) have long been perplexing, from its first discovery to the latest clinical trials of recombinant AAV (rAAV) therapy. Wild-type AAV (wtAAV) does not cause any known disease, making it an ideal vector for gene therapy, as viral vectors retain virus-like properties. Although AAV stimulates only a mild immune response compared to other viruses, it is still recognized by the innate immune system and induces adaptive immune responses. B cell responses against both wtAAV and rAAV are robust and can hinder gene therapy applications and prevent redosing. T-cell responses can clear transduced cells or establish tolerance against gene therapy. Immune responses to AAV gene therapy are influenced by many factors. Most clinical immunotoxicities that develop in response to gene therapies have emerged as higher doses of AAV vectors have been utilized and were not properly modeled in pre-clinical animal studies. Thus, several strategies have been undertaken to reduce or mitigate immune responses to AAV. While we have learned a considerable amount about how the immune system responds to AAV gene therapy since the discovery of AAV virus, it still remains a curious case that requires more investigation to fully understand.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-dose intranasal AdC68-vectored vaccines rapidly protect Syrian hamsters against lethal Nipah virus infection.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-26 DOI: 10.1016/j.ymthe.2025.03.032

Mingqing Lu, Yanfeng Yao, Hang Liu, Yun Peng, Xuejie Li, Ge Gao, Miaoyu Chen, Xuekai Zhang, Lingjing Mao, Peipei Yang, XiaoYu Zhang, Jing Miao, Zhiming Yuan, Jiaming Lan, Chao Shan

{"title":"Single-dose intranasal AdC68-vectored vaccines rapidly protect Syrian hamsters against lethal Nipah virus infection.","authors":"Mingqing Lu, Yanfeng Yao, Hang Liu, Yun Peng, Xuejie Li, Ge Gao, Miaoyu Chen, Xuekai Zhang, Lingjing Mao, Peipei Yang, XiaoYu Zhang, Jing Miao, Zhiming Yuan, Jiaming Lan, Chao Shan","doi":"10.1016/j.ymthe.2025.03.032","DOIUrl":"10.1016/j.ymthe.2025.03.032","url":null,"abstract":"Nipah virus (NiV) infection is highly lethal in humans, and the development of vaccines that provide rapid protection is critical for addressing NiV outbreaks. In this study, we demonstrate that a single intranasal immunization with the chimpanzee adenoviral-vectored NiV vaccine, AdC68-F, induced robust and sustained cellular and humoral responses in BALB/c mice, and provided complete protection against challenge with the NiV-Malaysia strain (NiV-M) in Syrian hamsters. Notably, AdC68-F, administered at a dose of 5 × 109 viral particles, offered a complete prophylactic protection window as few as 7 days before exposure to a lethal NiV-M challenge. Furthermore, passive transfer of sera from AdC68-F or AdC68-G immunized animals conferred complete protection against NiV-M infection in naive hamsters. These findings underscore the pivotal role of antigen-specific immunity in controlling NiV infection and highlight the potential of single-dose intranasal AdC68-based NiV vaccines for rapid protection during outbreaks. By providing rapid and effective protection, these vaccines could help reduce human-to-human transmission and aid in curbing NiV outbreaks.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Living Myocardial Slices as Model for Testing Cardiac Pro-Reparative Gene Therapies.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-25 DOI: 10.1016/j.ymthe.2025.03.033

Rocco Caliandro, Azra Husetic, Merel L Ligtermoet, Arie R Boender, Lorena Zentilin, Gerard J J Boink, Mauro Giacca, Monika M Gladka

{"title":"Living Myocardial Slices as Model for Testing Cardiac Pro-Reparative Gene Therapies.","authors":"Rocco Caliandro, Azra Husetic, Merel L Ligtermoet, Arie R Boender, Lorena Zentilin, Gerard J J Boink, Mauro Giacca, Monika M Gladka","doi":"10.1016/j.ymthe.2025.03.033","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.033","url":null,"abstract":"Available models currently adopted for pre-clinical studies in the cardiovascular field either fail to recapitulate human cardiac physiology or are extremely expensive and time-consuming. Translational research would greatly benefit from the development of novel models that reflect the native mature phenotype of the human heart while being cost and time effective. Living myocardial slices (LMS) have emerged as a novel, powerful ex vivo tool for translational research. Although the number of studies adopting living myocardial slices is rapidly increasing, this model remains largely under-characterized. In this study, we make use of LMS and compare it to a murine model to deliver the cardioprotective factor Zinc finger E-box-binding homeobox 2 (ZEB2), a transcription factor known to exert cardioprotective effects after ischemic injury and promote the secretion of pro-angiogenetic factors Thymosin beta-4 (TMSB4) and Prothymosin alpha (PTMA). Our data show that viral-mediated delivery of these factors induced similar cardiomyocyte gene expression changes in LMS and mouse models. We also show that the delivery of these pro-angiogenic factors enhances an angiogenic response in both models, indicating that LMS are a suitable alternative to mice for studying the effects of gene transfer in various cardiac cell types.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-25 DOI: 10.1016/j.ymthe.2025.03.027

Paul R Sargunas, Emily Ariail, Raquel Lima E Silva, Akash Patil, Mingliang Zhang, Jikui Shen, Beatriz Silva Lopes, Yuseong Oh, Amelia C McCue, Ranjani Ramasubramanian, A Carson Stephenson, Aleksander S Popel, Peter A Campochiaro, Jamie B Spangler

{"title":"Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C.","authors":"Paul R Sargunas, Emily Ariail, Raquel Lima E Silva, Akash Patil, Mingliang Zhang, Jikui Shen, Beatriz Silva Lopes, Yuseong Oh, Amelia C McCue, Ranjani Ramasubramanian, A Carson Stephenson, Aleksander S Popel, Peter A Campochiaro, Jamie B Spangler","doi":"10.1016/j.ymthe.2025.03.027","DOIUrl":"10.1016/j.ymthe.2025.03.027","url":null,"abstract":"Several debilitating eye diseases that lead to vision loss are driven by ocular neovascularization, which entails abnormal blood vessel growth in the eye. Neovascularization is often induced by the upregulation of vascular endothelial growth factor (VEGF) ligands, which activate angiogenesis through engagement of VEGF receptor (VEGFR) proteins on endothelial cells. Therapeutic interventions that block ocular neovascularization by targeting VEGF ligands, particularly VEGF-A, have revolutionized eye disease treatment. However, a significant population of patients are either non-responders or develop resistance, which can be driven by the upregulation of other VEGF family ligands such as VEGF-C. Here, we engineered two bispecific receptor decoy fusion proteins that incorporate domains of VEGFR-1 and VEGFR-2 for more effective and comprehensive inhibition of VEGF ligands. We demonstrated that our engineered proteins bind all VEGF ligands and can sequester two ligands simultaneously. We further showed that these molecules block VEGF activity to potently inhibit proliferation, migration, and survival of human endothelial cells. Moreover, these receptor decoy proteins significantly reduced ocular neovascularization in two mouse models at doses wherein the current standard-of-care anti-VEGF therapy is ineffective. Collectively, our engineered receptor decoy proteins present a new architecture for VEGF pathway inhibition, offering a promising treatment paradigm for ocular diseases.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oncolytic Viruses as Cancer Therapeutics: From Mechanistic Insights to Clinical Translation.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-25 DOI: 10.1016/j.ymthe.2025.03.035

Akram Alwithenani, Pranaidej Hengswat, E Antonio Chiocca

{"title":"Oncolytic Viruses as Cancer Therapeutics: From Mechanistic Insights to Clinical Translation.","authors":"Akram Alwithenani, Pranaidej Hengswat, E Antonio Chiocca","doi":"10.1016/j.ymthe.2025.03.035","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.035","url":null,"abstract":"Oncolytic virotherapy is a therapeutic approach that leverages genetically engineered or naturally occurring viruses to selectively target and destroy cancer cells while sparing normal tissues. This review provides an overview of the mechanisms of action by oncolytic viruses (OVs), including direct oncolysis, immune activation, and tumor microenvironment (TME) modulation. Despite significant progress, challenges such as immune resistance, tumor evasion mechanisms, and delivery barriers continue to limit the efficacy of OVs. To address these obstacles, recent advances in OV engineering have focused on arming viruses with immunomodulatory molecules, utilizing tumor-specific promoters, and employing CRISPR-based genome editing. Emerging strategies, such as dual-targeting OVs and viral enhancer drugs, have demonstrated promising potential in preclinical and clinical settings. This review also highlights findings from recent clinical trials, underscoring the translational challenges in scaling OVs for widespread therapeutic application. By exploring these innovations and their implications, we aim to shed light on the future directions of oncolytic virotherapy and its transformative potential in cancer treatment.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical development of therapeutic mRNA applications.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-03-25 DOI: 10.1016/j.ymthe.2025.03.034

Magdalena M Żak, Lior Zangi

{"title":"Clinical development of therapeutic mRNA applications.","authors":"Magdalena M Żak, Lior Zangi","doi":"10.1016/j.ymthe.2025.03.034","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.03.034","url":null,"abstract":"mRNA therapeutics are emerging as a transformative approach in modern medicine, providing innovative, highly adaptable solutions for a wide range of diseases, from viral infections to cancer. Since the approval of the first mRNA therapeutic-the COVID-19 vaccines in 2021-we have identified over 70 current clinical trials utilizing mRNA for various diseases. We propose classifying mRNA therapeutics into three main categories: vaccines, protein replacement therapies, and therapeutic antibodies. Each category can be further divided into subcategories. Vaccines include those targeting viral antigens, bacterial or parasitic antigens, general and individualized cancer antigens, and self-antigens. Protein replacement therapies include maintenance therapeutics designed to treat genetic disorders and interventional therapeutics, where delivering therapeutic proteins could improve patient outcomes, such as VEGF-A for ischemic heart disease or proinflammatory cytokines in cancer. Therapeutic antibodies are based on mRNA sequences encoding the heavy and light chains of clinically relevant antibodies, enabling patient cells to produce them directly, bypassing the costly and complex process of manufacturing protein-ready antibodies. Another category of mRNA-based therapeutics encompasses cell and gene therapies, including CRISPR with mRNA-mediated delivery of Cas9 and the in vivo generation of cells expressing CAR through mRNA. We discuss examples of mRNA therapeutics currently in clinical trials within each category, providing a comprehensive overview of the field's progress and highlighting key advancements as of the end of 2024.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0