Current opinion in biotechnology最新文献

英文中文

Engineering next-generation chimeric antigen receptor-T cells: recent breakthroughs and remaining challenges in design and screening of novel chimeric antigen receptor variants 下一代嵌合抗原受体-T 细胞工程：设计和筛选新型嵌合抗原受体变体的最新突破和仍然面临的挑战。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-11-05 DOI: 10.1016/j.copbio.2024.103223

Anna Mei , Kevin P Letscher , Sai Reddy

Chimeric antigen receptor (CAR) T cells are a powerful treatment against hematologic cancers. The functional phenotype of a CAR-T cell is influenced by the domains that comprise the synthetic receptor. Typically, the potency of therapeutic CAR-T cell candidates is assessed by preclinical functional assays and mouse models (i.e. human tumor xenografts). However, to date, only a few sets of domains (e.g. CD8, CD28, 41BB) have been extensively tested in preclinical assays and human clinical studies. To characterize the efficiency of a CAR, different assays have been utilized to analyze T cell phenotypes, such as expansion, cytotoxicity, secretome, and persistence. However, each of these previous studies evaluated the importance of an assay differently, resulting in a wide range of functionally diverse CARs. In this review, we highlight recent (high-throughput) methods to analyze CAR domains and demonstrate their impact on inducing T cell phenotypes and activity. We also describe advances in computational methods and their potential for identifying CAR variants with enhanced properties. Finally, we reflect on the need for a standardized scoring system to support the clinical development of next-generation CARs.

嵌合抗原受体（CAR）T 细胞是一种治疗血液癌症的有效方法。CAR-T 细胞的功能表型受合成受体结构域的影响。通常，临床前功能测定和小鼠模型（即人类肿瘤异种移植）可评估候选 CAR-T 治疗细胞的效力。然而，迄今为止，只有少数几个结构域（如 CD8、CD28、41BB）在临床前试验和人体临床研究中进行了广泛测试。为了描述 CAR 的效率，人们采用了不同的检测方法来分析 T 细胞的表型，如扩增、细胞毒性、分泌组和持久性。然而，以往的这些研究对检测方法重要性的评估各不相同，因此产生了多种功能各异的 CAR。在这篇综述中，我们重点介绍了最近分析 CAR 结构域的（高通量）方法，并展示了它们对诱导 T 细胞表型和活性的影响。我们还介绍了计算方法的进展及其在鉴定具有增强特性的 CAR 变体方面的潜力。最后，我们探讨了建立标准化评分系统以支持下一代 CAR 临床开发的必要性。

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引用次数: 0

Review: can bioelectrochemical sensors be used to monitor soil microbiome activity and fertility? 回顾：生物电化学传感器能否用于监测土壤微生物组的活动和肥力？

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-11-05 DOI: 10.1016/j.copbio.2024.103222

Christina F Webster , Won-Jun Kim , Gemma Reguera , Maren L Friesen , Haluk Beyenal

This review presents current knowledge on applying bioelectrochemical sensors to monitor soil fertility through microbial activity and discusses future perspectives. Soil microbial activity is considered an indicator of soil fertility due to the interconnected relationship between soil nutrient composition, microbiome, and plant productivity. Similarities between soils and bioelectrochemical reactors provide the foundation for the design of bioelectrochemical sensors driven by microorganisms enriched as electrochemically active biofilms on polarized electrodes. The biofilm can exchange electrons with electrodes and metabolites with the nearby microbiome to generate electrochemical signals that inform of microbiome functions and nutrient bioavailability. Such mechanisms can be harnessed as a bioelectrochemical sensor for proxy monitoring of soil fertility to address the need for real-time monitoring of soils.

本综述介绍了应用生物电化学传感器通过微生物活动监测土壤肥力的现有知识，并讨论了未来的发展前景。由于土壤养分组成、微生物群和植物生产力之间的相互关系，土壤微生物活动被认为是土壤肥力的一个指标。土壤与生物电化学反应器之间的相似性为设计生物电化学传感器奠定了基础，该传感器由极化电极上富含电化学活性生物膜的微生物驱动。生物膜可以与电极交换电子，并与附近的微生物群交换代谢物，从而产生电化学信号，为微生物群功能和营养物质生物利用率提供信息。可以利用这种机制作为生物电化学传感器，对土壤肥力进行代理监测，以满足对土壤进行实时监测的需要。

引用次数: 0

Engineering T-cell receptor–like antibodies for biologics and cell therapy 为生物制剂和细胞疗法设计类 T 细胞受体抗体。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-11-04 DOI: 10.1016/j.copbio.2024.103224

Lene S Høydahl , Gøril Berntzen, Geir Å Løset

A major prevailing challenge limiting our ability to fully harness the potential of the latest-generation therapeutic antibodies is the scarcity of clinically established disease-specific targets. A major next step forward will therefore be to expand this target space. The recent clinical success of immunotherapies such as adoptive T-cell transfer, immune checkpoint inhibition, and chimeric antigen receptor (CAR) T-cell therapy strongly supports focusing on the immunopeptidome of peptides presented by human leukocyte antigen (pHLA) that are normally surveilled by T-cell receptors (TCRs). Directing novel antibody development toward pHLA targets has given rise to TCR-like antibodies, which reached the clinic in 2020, as both bispecific T-cell engaging antibodies and the CARs of CAR-T cell therapies. In this review, we highlight recent advances in TCR-like antibodies, including therapeutic modalities, engineering strategies, and benchmarks for success.

限制我们充分利用最新一代治疗性抗体潜力的一个主要挑战是，临床上确定的疾病特异性靶点很少。因此，下一步的主要工作就是扩大这一靶点的范围。最近，免疫疗法（如收养 T 细胞转移、免疫检查点抑制和嵌合抗原受体（CAR）T 细胞疗法）在临床上取得了成功，这有力地支持了将重点放在人类白细胞抗原（pHLA）呈现的肽的免疫肽组上，这些肽通常由 T 细胞受体（TCR）监测。针对 pHLA 靶点的新型抗体开发催生了类 TCR 抗体，它们作为双特异性 T 细胞参与抗体和 CAR-T 细胞疗法的 CAR，于 2020 年进入临床。在这篇综述中，我们将重点介绍 TCR 类抗体的最新进展，包括治疗模式、工程策略和成功基准。

引用次数: 0

Albumin-based strategies to effectively prolong the circulation half-life of small immunomodulatory payloads in cancer therapy 在癌症治疗中有效延长小型免疫调节有效载荷循环半衰期的基于白蛋白的策略

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-31 DOI: 10.1016/j.copbio.2024.103218

Sara Linciano , Emilia Vigolo , Antonio Rosato , Yoichi Kumada , Alessandro Angelini

Small immunomodulatory payloads (IMMs) such as peptide vaccines and cytokines have the capability to activate and boost the immune response against cancer. However, their clinical use has often been hindered by their poor stability and short circulating half-lives. To enhance the pharmacokinetic properties of small IMMs and promote their trafficking and accumulation in lymphatic and tumor tissues, a large variety of strategies have been developed. One of the most successful relies on the use of serum albumin (SA), the most abundant protein in the circulatory and lymphatic system. Here, we report a comparative analysis of the different covalent and noncovalent SA-based strategies applied so far to improve the efficacy of small IMMs in cancer therapy.

肽疫苗和细胞因子等小型免疫调节有效载荷（IMMs）具有激活和增强抗癌免疫反应的能力。然而，它们的稳定性差、循环半衰期短，往往阻碍了它们的临床应用。为了提高小型 IMMs 的药代动力学特性，促进它们在淋巴和肿瘤组织中的运输和积累，人们开发了多种策略。最成功的策略之一是使用血清白蛋白（SA），它是循环和淋巴系统中最丰富的蛋白质。在这里，我们报告了迄今为止为提高小型 IMMs 在癌症治疗中的疗效而应用的基于共价和非共价 SA 的不同策略的比较分析。

引用次数: 0

Editorial overview: Nanobiotechnology: A focus on the fundamentals 编辑综述：纳米生物技术：关注基本原理

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-26 DOI: 10.1016/j.copbio.2024.103220

Warren C.W. Chan

引用次数: 0

Sharp solutions to cleave plant fibers 切割植物纤维的锐利解决方案。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-24 DOI: 10.1016/j.copbio.2024.103219

Talia Jacobson , Mair Edwards , Cătălin Voiniciuc

Plant cells sequester atmospheric carbon in thick walls containing heterogenous networks of cellulose and hemicelluloses (e.g. xylan and mannan), surrounded by additional polymers. Plants and microbes secrete glycosyl hydrolases that act alone or as modular complexes to modify extracellular polysaccharides. While several carbohydrate-active enzymes have been successfully targeted for crop improvement, additional hydrolytic proteins or more efficient versions are needed for the circular bioeconomy. Here, we discuss persistent challenges and emerging opportunities to enhance extracellular enzymes for use in plants or as tools to process biomass for various products. In addition to the design of minimal cellulosomes that combine microbial scaffolding proteins and polysaccharide-degrading enzymes, we review three major strategies that could improve the properties of plant-derived glycosyl hydrolases.

植物细胞将大气中的碳封存在由纤维素和半纤维素（如木聚糖和甘露聚糖）组成的异质网络的厚壁中，周围还有其他聚合物。植物和微生物分泌的糖基水解酶可单独或以模块化复合物的形式改变细胞外多糖。虽然有几种碳水化合物活性酶已被成功用于作物改良，但循环生物经济还需要更多的水解蛋白或更高效的水解酶。在此，我们将讨论如何增强细胞外酶在植物中的应用或将其作为加工生物质以生产各种产品的工具所面临的挑战和新出现的机遇。除了设计结合微生物支架蛋白和多糖降解酶的最小纤维素体外，我们还回顾了可改善植物源糖基水解酶特性的三大策略。

引用次数: 0

The expansion of fungal organisms in environmental biotechnology 扩大真菌生物在环境生物技术中的应用。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-24 DOI: 10.1016/j.copbio.2024.103217

Korena K Mafune , Mari KH Winkler

Fungal organisms hold vital roles in ecosystem processes. Despite their intricate entanglement with most life on earth and their powerful metabolic capacities, they remain under-represented in environmental biotechnology. The interest in applying fungal biotechnologies to different environments is growing, as light is shed on their versatile potential. A diversity of fungi can be harnessed to promote crop yield, remediate pollutants from terrestrial and aquatic environments, and mitigate climate change impacts. Current technological advancements, such as the increase in high-accuracy ‘omics pipelines, provide improvement. However, it is emphasized that there are many knowledge gaps regarding applying fungal biotechnology at scale where other organisms are inherently present. Hence, there is a dire need to increase funding that enables in-depth studies on fungal processes, such as degradation capacities, metabolite production, and cross-kingdom interactions, that promote climate-smart biotechnologies.

真菌生物在生态系统过程中发挥着至关重要的作用。尽管真菌与地球上大多数生命错综复杂地纠缠在一起，而且具有强大的新陈代谢能力，但它们在环境生物技术中的代表性仍然不足。随着人们对真菌多功能潜力的了解，将真菌生物技术应用于不同环境的兴趣与日俱增。可以利用真菌的多样性来提高作物产量、修复陆地和水生环境中的污染物以及减轻气候变化的影响。当前的技术进步，如高精度'omics'管道的增加，提供了改进的机会。但需要强调的是，在大规模应用真菌生物技术方面还存在许多知识空白，而这些生物技术本身就存在于其他生物体中。因此，亟需增加资金投入，以便深入研究真菌的降解能力、代谢物产生和跨领域相互作用等过程，促进气候智能生物技术的发展。

引用次数: 0

Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery 高通量嵌合抗原受体 T 细胞发现的挑战和未来展望。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-21 DOI: 10.1016/j.copbio.2024.103216

Savannah E Butler , Margaret E Ackerman

Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for in vivo efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.

目前正在开发新型嵌合抗原受体（CAR）T细胞设计，以克服肿瘤识别、贩运、靶上但非肿瘤结合、细胞毒性、持久性以及肿瘤微环境中的免疫抑制等难题。传统的 CAR 工程是一个迭代、假设驱动的过程，在这个过程中，新的设计被合理地构建并测试体内疗效，我们借鉴了基于小分子和蛋白质的治疗发现领域的经验，同时考虑了高通量功能筛选技术如何开始应用于开发有前景的 CAR 候选者。我们回顾了高通量筛选方法的开发是如何简化 CAR 发现过程，最终提高效率和临床疗效的。

引用次数: 0

Proteomics insights into the fungal-mediated bioremediation of environmental contaminants 蛋白质组学对真菌介导的环境污染物生物修复的启示。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-10 DOI: 10.1016/j.copbio.2024.103213

Kshitija Shah , Soham Ray , Himadri Bose , Vijaya Pandey , James A Wohlschlegel , Shaily Mahendra

As anthropogenic activities continue to introduce various contaminants into the environment, the need for effective monitoring and bioremediation strategies is critical. Fungi, with their diverse enzymatic arsenal, offer promising solutions for the biotransformation of many pollutants. While conventional research reports on ligninolytic, oxidoreductive, and cytochrome P450 (CYP) enzymes, the vast potential of fungi, with approximately 10 345 protein sequences per species, remains largely untapped. This review describes recent advancements in fungal proteomics instruments as well as software and highlights their detoxification mechanisms and biochemical pathways. Additionally, it highlights lesser-known fungal enzymes with potential applications in environmental biotechnology. By reviewing the benefits and challenges associated with proteomics tools, we hope to summarize and promote the studies of fungi and fungal proteins relevant in the environment.

随着人类活动不断向环境中引入各种污染物，有效的监测和生物修复策略显得至关重要。真菌拥有多种酶库，为许多污染物的生物转化提供了前景广阔的解决方案。传统的研究报告涉及木质素分解酶、氧化还原酶和细胞色素 P450 (CYP) 酶，而真菌的巨大潜力（每个物种约有 10 345 个蛋白质序列）在很大程度上仍未得到开发。本综述介绍了真菌蛋白质组学仪器和软件的最新进展，并重点介绍了真菌的解毒机制和生化途径。此外，它还重点介绍了鲜为人知的、具有环境生物技术应用潜力的真菌酶。通过回顾与蛋白质组学工具相关的益处和挑战，我们希望总结并促进与环境相关的真菌和真菌蛋白质研究。

引用次数: 0

Methane to bioproducts: unraveling the potential of methanotrophs for biomanufacturing 从甲烷到生物产品：揭示甲烷营养体在生物制造方面的潜力。

IF 7.1 2区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS

Current opinion in biotechnology

Pub Date : 2024-10-04 DOI: 10.1016/j.copbio.2024.103210

Justin N Tan , Keshav Ratra , Steven W Singer , Blake A Simmons , Shubhasish Goswami , Deepika Awasthi

With the continuous increase in the world population, anthropogenic activities will generate more waste and create greenhouse gases such as methane, amplifying global warming. The biological conversion of methane into biochemicals is a sustainable solution to sequester and convert this greenhouse gas. Methanotrophic bacteria fulfill this role by utilizing methane as a feedstock while manufacturing various bioproducts. Recently, methanotrophs have made their mark in industrial biomanufacturing. However, unlike glucose-utilizing model organisms such as Escherichia coli and Saccharomyces cerevisiae, methanotrophs do not have established transformation methods and genetic tools, making these organisms challenging to engineer. Despite these challenges, recent advancements in methanotroph engineering demonstrate great promise, showcasing these C1-carbon-utilizing microbes as prospective hosts for bioproduction. This review discusses the recent developments and challenges in strain engineering, biomolecule production, and process development methodologies in the methanotroph field.

随着世界人口的不断增加，人类活动将产生更多的废物，并产生甲烷等温室气体，加剧全球变暖。通过生物转化将甲烷转化为生化物质是封存和转化这种温室气体的可持续解决方案。养甲烷细菌利用甲烷作为原料，制造各种生物产品，从而发挥了这一作用。最近，甲烷营养细菌在工业生物制造领域大显身手。然而，与大肠杆菌和酿酒酵母等利用葡萄糖的模式生物不同，甲烷营养菌没有成熟的转化方法和遗传工具，因此这些生物的工程设计具有挑战性。尽管存在这些挑战，但最近在甲烷营养体工程学方面取得的进展展示了巨大的前景，表明这些 C1 碳利用微生物有望成为生物生产的宿主。本综述讨论了甲烷营养体领域在菌种工程、生物大分子生产和工艺开发方法方面的最新进展和挑战。

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Current opinion in biotechnology

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