{"title":"Oral delivery of therapeutic peptides by milk-derived extracellular vesicles","authors":"Spencer R. Marsh, Robert G. Gourdie","doi":"10.1038/s44222-024-00227-9","DOIUrl":"10.1038/s44222-024-00227-9","url":null,"abstract":"The oral delivery of difficult-to-drug molecules, such as peptides, can be achieved using milk-derived extracellular vesicles. The Tiny Cargo Company has established a workflow for the large-scale production of extracellular vesicles from milk for the development of XoLacta — an oral therapy that mitigates the side effects of radiation therapy.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 10","pages":"806-807"},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chimeric brain organoids","authors":"Caroline Beyer","doi":"10.1038/s44222-024-00229-7","DOIUrl":"10.1038/s44222-024-00229-7","url":null,"abstract":"An article in Nature reports the generation of human chimeric brain organoids that integrate cells from multiple donors.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 8","pages":"635-635"},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetically engineered hypoimmunogenic cell therapy","authors":"Akitsu Hotta, Sonja Schrepfer, Andras Nagy","doi":"10.1038/s44222-024-00219-9","DOIUrl":"10.1038/s44222-024-00219-9","url":null,"abstract":"Immune rejection is an important obstacle to the use of allogeneic ‘off-the-shelf’ cells for transplantation into immunocompetent patients. Genetic modification has emerged as a promising approach to improve immune compatibility in various applications, including cancer immunotherapy and stem cell-based therapies. Several approaches have been proposed to evade the recognition and attack of transplanted cells by specific host immune cells; however, further investigation is needed to ensure the hypoimmunity and safety of cell-based therapies in clinical practice. This Review discusses key advances and challenges in the clinical translation of hypoimmunogenic cells and describes the genetic engineering methods and manufacturing processes used to create hypoimmunogenic therapeutic cells, while highlighting the complexity of relevant immunological pathways. To overcome the immune rejection issue in allogeneic cell transplants, various genetic engineering strategies have been developed. This Review explores these advances and discusses challenges in evading immune responses, as well as considerations for clinical development.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 11","pages":"960-979"},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantitative synthetic biology","authors":"Nan Luo, Guoping Zhao, Chenli Liu","doi":"10.1038/s44222-024-00224-y","DOIUrl":"10.1038/s44222-024-00224-y","url":null,"abstract":"Synthetic biology faces major challenges in the rational design of complex living systems, necessitating a quantitative understanding of the principles that guide the emergence of functions from biological building blocks. Here, we propose quantitative synthetic biology as a new research paradigm, integrating quantitative biology, systems biology and synthetic biology.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 11","pages":"911-913"},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanie Generali, Yoshihiko Fujita, Debora Kehl, Moe Hirosawa, Maximilian Y. Emmert, Jun Takahashi, Simon P. Hoerstrup, Hirohide Saito
{"title":"Purification technologies for induced pluripotent stem cell therapies","authors":"Melanie Generali, Yoshihiko Fujita, Debora Kehl, Moe Hirosawa, Maximilian Y. Emmert, Jun Takahashi, Simon P. Hoerstrup, Hirohide Saito","doi":"10.1038/s44222-024-00220-2","DOIUrl":"10.1038/s44222-024-00220-2","url":null,"abstract":"The reprogramming of somatic cells into induced pluripotent stem cells using Yamanaka factors has revolutionized biomedical research. In the past few years, substantial advances have been made in differentiating them into a variety of different cell types, including neurons, cardiomyocytes, megakaryocytes, endothelial cells, β-pancreatic cells and more. Today, these cells are ready to be used for clinical purposes in regenerative medicine and disease modelling to explore and pinpoint new therapeutic approaches. Nonetheless, before these therapies are ready for practical application, we must ensure the quality and integrity of the cells employed in various uses. Thus, it is essential to possess well-characterized and high-quality purified cell populations. In this Review, we discuss the latest applicable cell purification methods for clinical preparations, encompassing both current technologies that have been used in clinical settings and emerging state-of-the-art approaches that promise even greater potential. This Review explores the principles and applications of cell purification technologies, with a particular emphasis on their clinical relevance for pluripotent stem-cell-based therapies. The authors discuss current technologies and emerging state-of-the-art approaches that promise even greater potential.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 11","pages":"930-943"},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141743118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microrobots neutralize proinflammatory cytokines in the gut","authors":"Christine-Maria Horejs","doi":"10.1038/s44222-024-00228-8","DOIUrl":"10.1038/s44222-024-00228-8","url":null,"abstract":"An article in Science Robotics reports green algae-based microrobots, carrying macrophage membrane-coated nanoparticles, that can be orally administered to neutralize proinflammatory cytokines in the gastrointestinal tract to treat inflammatory bowel disease.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 8","pages":"636-636"},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141743117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruofei Zhang, Bing Jiang, Kelong Fan, Lizeng Gao, Xiyun Yan
{"title":"Designing nanozymes for in vivo applications","authors":"Ruofei Zhang, Bing Jiang, Kelong Fan, Lizeng Gao, Xiyun Yan","doi":"10.1038/s44222-024-00205-1","DOIUrl":"10.1038/s44222-024-00205-1","url":null,"abstract":"Biocatalytic drugs, including natural and artificial enzymes that can accelerate biochemical reactions, are promising tools to address redox imbalances, metabolic disorders and immune dysregulations. However, these types of drugs suffer from uncontrolled activity, limited stability, heightened immunogenicity, lack of targeted action and adverse effects, which limit their clinical application. Preclinical results suggest that nanozymes, a new class of biocatalysts, could help overcome these challenges. In this Review, we discuss nanozymes for the regulation of reactive oxygen species in vivo. We first elucidate the fundamental mechanisms governing nanozyme-driven biocatalytic reactions in disease treatment. We then discuss the application of nanozymes in treating pathological disorders such as exogenous oxidative damage, inflammatory diseases, neurological disorders, tumours and bacterial infection. The design criteria for nanozymes to perform biocompatible and tightly regulated catalysis at targeted lesions are further highlighted. Finally, we explore the prospects, challenges and opportunities for clinical translation of nanozymes. Nanozymes are nanomaterials that exert biocatalytic functions within biological systems. This Review discusses the design criteria and mechanisms of nanozymes for in vivo applications to treat different pathological disorders.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 10","pages":"849-868"},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141743119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guglielmo Lanzani, Greta Chiaravalli, Elisabetta Colombo, Giovanni Manfredi, Stefano Di Marco, Vito Vurro, Fabio Benfenati
{"title":"Nanotechnology for vision restoration","authors":"Guglielmo Lanzani, Greta Chiaravalli, Elisabetta Colombo, Giovanni Manfredi, Stefano Di Marco, Vito Vurro, Fabio Benfenati","doi":"10.1038/s44222-024-00210-4","DOIUrl":"10.1038/s44222-024-00210-4","url":null,"abstract":"Degenerative retinal dystrophies, such as retinitis pigmentosa and age-related macular degeneration, cause the progressive loss of retinal photoreceptors, which leads to blindness. Thus far, pharmacological treatments have failed to cure or effectively block the progression of these diseases. One possible solution is to replace photoreceptors with retinal prostheses; however, inorganic electronic devices have not yet achieved satisfactory results in replicating natural vision. Nanotechnology, benefitting from low invasiveness and wireless stimulation, may overcome many of the challenges presented by electronic retinal devices. In particular, nanoparticles can be engineered to harvest and transduce light energy into bioelectricity, mimicking the behaviour of natural photoreceptors. In this Review, we discuss nanotechnology strategies for vision restoration, highlighting nanomedicine approaches in relation to clinically applied therapeutic strategies for retinal degeneration. We further explore the clinical potential of nanotechnology for vision restoration and the challenges that remain to be overcome. Degenerative retinal dystrophies, such as retinitis pigmentosa and age-related macular degeneration, lead to blindness owing to the progressive damage of retinal photoreceptors. This Review discusses nanotechnology-based treatment approaches for vision restoration.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 10","pages":"829-848"},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141743231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lily Li-Wen Wang, Yongsheng Gao, Zhaoqianqi Feng, David J. Mooney, Samir Mitragotri
{"title":"Designing drug delivery systems for cell therapy","authors":"Lily Li-Wen Wang, Yongsheng Gao, Zhaoqianqi Feng, David J. Mooney, Samir Mitragotri","doi":"10.1038/s44222-024-00214-0","DOIUrl":"10.1038/s44222-024-00214-0","url":null,"abstract":"Cell therapies, such as immune cell and stem cell therapies, are being preclinically and clinically explored for the treatment of various diseases, but are often limited by low efficacy and safety concerns. Drug delivery systems at the nanoscale, microscale and macroscale can be designed to improve cell therapies by optimizing pharmacokinetics, cell function and cell viability, and by preventing cell exhaustion and immunogenicity. In this Review, we discuss the engineering of drug delivery systems at various scales to improve the biological functions of therapeutic cells, modulate tissue environments to promote the survival and efficacy of therapeutic cells, enable targeted delivery of therapeutic agents by transferred cells and provide protective barriers for cells in vivo. We further outline crucial milestones for the clinical translation of cell therapies integrated with drug delivery systems and highlight manufacturing challenges. Drug delivery systems can be integrated with cell therapies to improve the efficacy and safety of therapeutic cells. This Review discusses the design of nanoscale, microscale and macroscale drug delivery systems for precise cell modulation, targeted cell and cargo delivery and cell protection.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 11","pages":"944-959"},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Striking the simplicity–complexity balance","authors":"","doi":"10.1038/s44222-024-00216-y","DOIUrl":"10.1038/s44222-024-00216-y","url":null,"abstract":"Bioengineering breakthroughs often arise from deceptively simple solutions, leveraging scalability, modularity and ease-of-use. However, certain biomedical applications require the integration of custom-engineered, patient-specific complexity. Striking this simplicity–complexity balance will drive affordable, globalized health innovations.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"2 7","pages":"531-531"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44222-024-00216-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141608121","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}
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