{"title":"To cut or not to cut: Next-generation genome editors for precision genome engineering","authors":"Meng Zhang , Zhixin Zhu , Guanhua Xun , Huimin Zhao","doi":"10.1016/j.cobme.2023.100489","DOIUrl":"10.1016/j.cobme.2023.100489","url":null,"abstract":"<div><p>Since the original report of repurposing the CRISPR/Cas9 system for genome engineering, the past decade has witnessed profound improvement in our ability to efficiently manipulate the mammalian genome. However, significant challenges lie ahead that hinder the translation of CRISPR-based gene editing technologies into safe and effective therapeutics. The CRISPR systems often have a limited target scope due to PAM restrictions, and the off-target activity also poses serious risks for therapeutic applications. Moreover, the first-generation genome editors typically achieve desired genomic modifications by inducing double-strand breaks (DSBs) at target site(s). Despite being highly efficient, this “cut and fix” strategy is less favorable in clinical settings due to drawbacks associated with the nuclease-induced DSBs. In this review, we focus on recent advances that help address these challenges, including the engineering and discovery of novel CRISPR/Cas systems with improved functionalities and the development of DSB-free genome editors.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100489"},"PeriodicalIF":3.9,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anatomics: Co-engineering body and machine in pursuit of synergistic bionic performance","authors":"Tyler R. Clites","doi":"10.1016/j.cobme.2023.100490","DOIUrl":"10.1016/j.cobme.2023.100490","url":null,"abstract":"<div><p>Bionic devices have the potential to transform human mobility. For this promise to be fully realized, it is important that the body and machine elements of bionic systems be seamlessly integrated. One challenge to this level of integration is that the majority of development efforts are focused on the machine, while the body is left unaltered. This leads to suboptimal body–machine interactions, which limits the efficacy of the bionic system. In this review, I explore an alternative design paradigm, which I call “anatomics,” in which body and machine are engineered in parallel. I highlight historical and recent examples of anatomics as applied to clinical problems, and discuss how these approaches have enabled the field of bionics to make progress in overcoming long-standing challenges. I also attempt to demystify the anatomics process by outlining the most important lessons I have learned while working in this space.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100490"},"PeriodicalIF":3.9,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42476046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current opinion: Underreported cell populations in the aortic valve influence tissue development and homeostasis","authors":"Daniel Chaparro , Joshua D. Hutcheson","doi":"10.1016/j.cobme.2023.100486","DOIUrl":"10.1016/j.cobme.2023.100486","url":null,"abstract":"<div><p>During valvulogenesis, various cells in the developing heart remodel the cushions in the outflow tract to shape the aortic valve (AoV). In adulthood, mature cells maintain the tissue in homeostatic balance to cope with changes in cardiac mechanics. Pathological progression of aortic valve disease is characterized by asymptomatic irreversible extracellular matrix (ECM) remodeling rendering the valve dysfunctional, ultimately leading to heart failure and death if the valve is not replaced. Resident cells within the tissue are responsible for congenital and acquired pathological conditions. A complex heterogenous population of cells resides within the valve apparatus, including underreported populations of neurons and melanocytes. Though not thoroughly explored, reports suggest that these cell types have implications in development, homeostasis, and disease progression within the AoV. In this current opinion piece, we summarize recent and relevant literature exploring the connection between both AoV cellular heterogeneity and cell developmental origin in development and disease.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100486"},"PeriodicalIF":3.9,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41973653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sayantan Tripathy , Suhash Chavva , Gerard L. Coté , Samuel Mabbott
{"title":"Modular and handheld Raman systems for SERS-based point-of-care diagnostics","authors":"Sayantan Tripathy , Suhash Chavva , Gerard L. Coté , Samuel Mabbott","doi":"10.1016/j.cobme.2023.100488","DOIUrl":"10.1016/j.cobme.2023.100488","url":null,"abstract":"<div><p>This review highlights advancements in recent years concerning surface-enhanced Raman scattering approaches for point-of-care testing applications, with a particular emphasis on spectroscopic interrogation using modular and handheld Raman systems. The surge in interest in remote monitoring research, largely influenced by the coronavirus disease 2019 pandemic, has underscored inconsistencies in the application of the term ‘point-of-care.’ This term is particularly misused when large, centralized lab types of static spectrometers are employed, which contradicts the principle of near-patient testing. We address this contradiction by spotlighting research that employs portable spectrometers, thus pushing the boundaries for future in-field use and emphasizing their potential to enhance point-of-care testing capabilities.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100488"},"PeriodicalIF":3.9,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47136546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Towards ultrasound imaging-based closed-loop peripheral nerve stimulation for tremor suppression","authors":"Nitin Sharma , Xiangming Xue , Ashwin Iyer , Xiaoning Jiang , Daniel Roque","doi":"10.1016/j.cobme.2023.100484","DOIUrl":"10.1016/j.cobme.2023.100484","url":null,"abstract":"<div><p>Despite several decades of research investigating the use of peripheral electrical stimulation (ES) for tremor suppression in an upper limb, ES design for effective tremor suppression remains elusive. The article reviews sensing approaches to measure limb tremors and existing musculoskeletal models of tremor and their use in closed-loop suppression control. We also motivate a case for incorporating ultrasound (US) imaging into the closed-loop control for increased tremor suppression efficacy. When combined with wearable US transducers, the novel approach could be a promising technique to advance musculoskeletal models that investigate tremor mechanisms and new ES closed-loop techniques with personalized stimulation parameters for tremor suppression.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100484"},"PeriodicalIF":3.9,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46809584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S.S.V. Tetali, A.T.R. Fricker, Y.A. van Domburg, I. Roy
{"title":"Intelligent biomaterials for cardiovascular applications","authors":"S.S.V. Tetali, A.T.R. Fricker, Y.A. van Domburg, I. Roy","doi":"10.1016/j.cobme.2023.100474","DOIUrl":"10.1016/j.cobme.2023.100474","url":null,"abstract":"<div><p>Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, and as such, research in cardiovascular medicine is continuously evolving. Recent advances in technology have created opportunities for improving the diagnosis and management of cardiovascular disease. This review article summarizes the use of innovative polymeric biomaterials for various cardiovascular applications, highlighting promising results obtained in the past five years.</p><p>The review begins by discussing the use of artificial blood vessels and coronary artery stents with biosensors for coronary artery disease management. Additionally, the studies on cardiac patches for heart failure management are evaluated. The review also covers recent advancements in artificial intelligence and real-time health monitoring for diagnosing cardiovascular conditions such as arrhythmias and structural heart disease. New catheters for epicardial mapping and stretchable conducting polymers for surface electrodes have improved diagnostic capabilities. The review also examines advancements in engineering with intelligent biomaterials for unique and sustainable treatment options. This includes piezoelectric and triboelectric nanogenerators for improved cardiovascular devices, reducing the need for battery changes and the risk of infections.</p><p>Overall, the review provides a comprehensive analysis of innovative polymeric biomaterials for various cardiovascular diagnostic and treatment modalities. It summarizes recent studies that demonstrate the potential of these materials for improving patient outcomes and ultimately reducing the burden of cardiovascular disease. As the field of cardiovascular medicine continues to evolve, these advancements may pave the way for further progress in the diagnosis and management of cardiovascular disease.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100474"},"PeriodicalIF":3.9,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45077881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterizing off-target effects of genome editors","authors":"Xichen Rao , Huanan Zhao , Chuyun Shao , Chengqi Yi","doi":"10.1016/j.cobme.2023.100480","DOIUrl":"10.1016/j.cobme.2023.100480","url":null,"abstract":"<div><p>Programmable base editors and prime editors offer the potential for highly efficient and precise genome manipulation. However, in order to safely apply these editors in clinical settings, it is essential to comprehensively characterize their off-target effects. In this review, we introduce some representative technologies for assessing off-target effects on both the genome and transcriptome and gain insight into the off-target effects of these genome editors. Importantly, we also discuss the limitations of the current off-target assessment methods for both <em>ex vivo</em> and <em>in vivo</em> biomedical applications and highlight the need to develop comprehensive and tailored off-target assessing methods which will be crucial for advancing the safe and effective gene editing applications launched by therapeutic companies and research groups.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100480"},"PeriodicalIF":3.9,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47247060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection and quantification of unintended large on-target gene modifications due to CRISPR/Cas9 editing","authors":"So Hyun Park, Mingming Cao, Gang Bao","doi":"10.1016/j.cobme.2023.100478","DOIUrl":"10.1016/j.cobme.2023.100478","url":null,"abstract":"<div><p>CRISPR/Cas9 based gene editing typically functions by creating a DNA double-strand break (DSB) at the intended target locus in a cell. Recent reports showed the occurrence of unintended on-target large gene modifications by CRISPR/Cas9-induced DSB, including large deletions, insertions, and chromosomal rearrangements, in addition to small insertions and deletions. These on-target large gene modifications can have high frequencies, undetectable by standard short-range PCR based assays, leading to data misinterpretation, reduced efficacy, and potential safety concerns in therapeutic gene editing. Here, we summarize the recent advances in analyzing large on-target gene editing outcomes and their implications to clinical application, and discuss opportunities for future improvements.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100478"},"PeriodicalIF":3.9,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44121229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Mujtaba , Arvind Negi , Alistair W.T. King , Mina Zare , Johana Kuncova-Kallio
{"title":"Surface modifications of nanocellulose for drug delivery applications; a critical review","authors":"Muhammad Mujtaba , Arvind Negi , Alistair W.T. King , Mina Zare , Johana Kuncova-Kallio","doi":"10.1016/j.cobme.2023.100475","DOIUrl":"https://doi.org/10.1016/j.cobme.2023.100475","url":null,"abstract":"<div><p>With the development of novel drugs and the discovery of new targets, there is an increased need for novel drug carriers. Nanocellulose has great potential to become a novel drug carrier thanks to its biocompatibility, low toxicity, tunable chemical structure, and sustainability. There are many types of nanocelluloses based on their physical properties (particle size, shape, surface charge), chemical properties (surface functional groups), form (lyophilized, hydrogel, aerogel, membrane) and source (bacterial, animal, plant) and that also largely influences drug release patterns, but also toxicity profile. To our knowledge, so far, no nanocellulose materials have been accepted as ingredients for pharmaceutical formulations. Some types of nanocellulose have however been accepted for use in medical devices, which is also a tightly regulated area. This review focuses on the modification of nanocellulose to enhance its capability as a drug delivery agent and pinpoints the pitfalls for the registration of such novel sustainable material.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100475"},"PeriodicalIF":3.9,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49817095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler C. Daniel , Hongzhi Zeng , Emmanuel C. Osikpa , Xue Gao
{"title":"Revolutionizing genetic disease treatment: Recent technological advances in base editing","authors":"Tyler C. Daniel , Hongzhi Zeng , Emmanuel C. Osikpa , Xue Gao","doi":"10.1016/j.cobme.2023.100472","DOIUrl":"10.1016/j.cobme.2023.100472","url":null,"abstract":"<div><p>Treating human genetic diseases has posed a significant and longstanding challenge to the medical community with traditional approaches often limited by their targeting scope, precision, and safety. In recent years, the development of Base Editors (BEs) has revolutionized the genome editing field, offering a precise and effective therapeutic option for correcting single nucleotide mutations responsible for more than half of human genetic diseases without causing unintended DNA damage. Since their invention in 2016, BEs have been successfully used in both research and clinical settings to treat many human genetic diseases, including sickle cell disease and amyotrophic lateral sclerosis. This review summarizes the most impactful developments in BE technology between 2020 and 2023, particularly emphasizing the methodology used to enhance this revolutionary tool. By offering a comprehensive overview of the latest advances in BE technology, we hope to provide a framework to accelerate future innovations in this field.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":"28 ","pages":"Article 100472"},"PeriodicalIF":3.9,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45706566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}